Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility

Dogan, Nergiz; Wu, Weisheng; Morrissey, Christapher S.; Chen, Kuan-Bei; Stonestrom, Aaron; Long, Maria; Keller, Cheryl A.; Cheng, Yong; Jain, Deepti; Visel, Axel; Pennacchio, Len A.; Weiss, Mitchell J.; Blobel, Gerd A.; Hardison, Ross C.

doi:10.1186/s13072-015-0009-5

Title: Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility

Journal Article · Thu Apr 23 00:00:00 EDT 2015 · Epigenetics & Chromatin

DOI:https://doi.org/10.1186/s13072-015-0009-5· OSTI ID:1190586

Dogan, Nergiz ^[1]; Wu, Weisheng ^[2]; Morrissey, Christapher S. ^[1]; Chen, Kuan-Bei ^[1]; Stonestrom, Aaron ^[3]; Long, Maria ^[1]; Keller, Cheryl A. ^[1]; Cheng, Yong ^[4]; Jain, Deepti ^[1]; Visel, Axel ^[5]; Pennacchio, Len A. ^[5]; Weiss, Mitchell J. ^[6]; Blobel, Gerd A. ^[3]; Hardison, Ross C. ^[1]

Pennsylvania State Univ., University Park, PA (United States)
Pennsylvania State Univ., University Park, PA (United States); Univ. of Michigan, Ann Arbor, MI (United States)
The Children’s Hospital of Philadelphia, Philadelphia, PA (United States); Univ. of Pennsylvania, Philadelphia, PA (United States)
Stanford University, Stanford, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DOE Joint Genome Institute, Walnut Creek, CA (United States)
St Jude Children’s Research Hospital, Memphis, TN (US)

Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the results of these and other studies. Results: TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. Conclusions: Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1190586

Journal Information:: Epigenetics & Chromatin, Vol. 8, Issue 16; ISSN 1756-8935

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 71 works

Citation information provided by
Web of Science

References (116)

Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes Siepel, A. Genome Research, Vol. 15, Issue 8 https://doi.org/10.1101/gr.3715005	journal	August 2005
Whole-Genome Shotgun Assembly and Analysis of the Genome of Fugu rubripes Aparicio, S. Science, Vol. 297, Issue 5585 https://doi.org/10.1126/science.1072104	journal	July 2002
Pioneer transcription factors: establishing competence for gene expression Zaret, K. S.; Carroll, J. S. Genes & Development, Vol. 25, Issue 21 https://doi.org/10.1101/gad.176826.111	journal	November 2011
Regulation of inducible and tissue-specific gene expression Maniatis, T.; Goodbourn, S.; Fischer, J. A. Science, Vol. 236, Issue 4806, p. 1237-1245 https://doi.org/10.1126/science.3296191	journal	June 1987
JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles Mathelier, Anthony; Zhao, Xiaobei; Zhang, Allen W. Nucleic Acids Research, Vol. 42, Issue D1 https://doi.org/10.1093/nar/gkt997	journal	November 2013
GREAT improves functional interpretation of cis-regulatory regions McLean, Cory Y.; Bristor, Dave; Hiller, Michael Nature Biotechnology, Vol. 28, Issue 5 https://doi.org/10.1038/nbt.1630	journal	May 2010
ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif Morikawa, Masato; Koinuma, Daizo; Tsutsumi, Shuichi Nucleic Acids Research, Vol. 39, Issue 20 https://doi.org/10.1093/nar/gkr572	journal	July 2011
Rapid and Pervasive Changes in Genome-wide Enhancer Usage during Mammalian Development Nord, Alex S.; Blow, Matthew J.; Attanasio, Catia Cell, Vol. 155, Issue 7 https://doi.org/10.1016/j.cell.2013.11.033	journal	December 2013
Highly Conserved Non-Coding Sequences Are Associated with Vertebrate Development Woolfe, Adam; Goodson, Martin; Goode, Debbie K. PLoS Biology, Vol. 3, Issue 1 https://doi.org/10.1371/journal.pbio.0030007	journal	November 2004
Differential genomic targeting of the transcription factor TAL1 in alternate haematopoietic lineages: Cell environment influences TAL1 genomic targeting Palii, Carmen G.; Perez-Iratxeta, Carolina; Yao, Zizhen The EMBO Journal, Vol. 30, Issue 3 https://doi.org/10.1038/emboj.2010.342	journal	December 2010
I B kinase (IKK ) regulates the balance between type I and type II interferon responses Ng, S. -L.; Friedman, B. A.; Schmid, S. Proceedings of the National Academy of Sciences, Vol. 108, Issue 52 https://doi.org/10.1073/pnas.1119137109	journal	December 2011
Lineage Regulators Direct BMP and Wnt Pathways to Cell-Specific Programs during Differentiation and Regeneration Trompouki, Eirini; Bowman, Teresa V.; Lawton, Lee N. Cell, Vol. 147, Issue 3 https://doi.org/10.1016/j.cell.2011.09.044	journal	October 2011
Detection of nonneutral substitution rates on mammalian phylogenies Pollard, K. S.; Hubisz, M. J.; Rosenbloom, K. R. Genome Research, Vol. 20, Issue 1 https://doi.org/10.1101/gr.097857.109	journal	October 2009
STATs Shape the Active Enhancer Landscape of T Cell Populations Vahedi, Golnaz; Takahashi, Hayato; Nakayamada, Shingo Cell, Vol. 151, Issue 5 https://doi.org/10.1016/j.cell.2012.09.044	journal	November 2012
The FoxA factors in organogenesis and differentiation Kaestner, Klaus H. Current Opinion in Genetics & Development, Vol. 20, Issue 5 https://doi.org/10.1016/j.gde.2010.06.005	journal	October 2010
ChIP-seq accurately predicts tissue-specific activity of enhancers Visel, Axel; Blow, Matthew J.; Li, Zirong Nature, Vol. 457, Issue 7231 https://doi.org/10.1038/nature07730	journal	February 2009
Histone H3K27ac separates active from poised enhancers and predicts developmental state Creyghton, M. P.; Cheng, A. W.; Welstead, G. G. Proceedings of the National Academy of Sciences, Vol. 107, Issue 50 https://doi.org/10.1073/pnas.1016071107	journal	November 2010
Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome Heintzman, Nathaniel D.; Stuart, Rhona K.; Hon, Gary Nature Genetics, Vol. 39, Issue 3 https://doi.org/10.1038/ng1966	journal	February 2007
Erythroid GATA1 function revealed by genome-wide analysis of transcription factor occupancy, histone modifications, and mRNA expression Cheng, Y.; Wu, W.; Ashok Kumar, S. Genome Research, Vol. 19, Issue 12 https://doi.org/10.1101/gr.098921.109	journal	November 2009
Evaluation of phylogenetic footprint discovery for predicting bacterial cis-regulatory elements and revealing their evolution Janky, Rekin's; van Helden, Jacques BMC Bioinformatics, Vol. 9, Issue 1 https://doi.org/10.1186/1471-2105-9-37	journal	January 2008
UniPROBE: an online database of protein binding microarray data on protein-DNA interactions Newburger, D. E.; Bulyk, M. L. Nucleic Acids Research, Vol. 37, Issue Database https://doi.org/10.1093/nar/gkn660	journal	January 2009
Genome-wide identification of TAL1's functional targets: Insights into its mechanisms of action in primary erythroid cells Kassouf, M. T.; Hughes, J. R.; Taylor, S. Genome Research, Vol. 20, Issue 8 https://doi.org/10.1101/gr.104935.110	journal	June 2010
Ubiquitous heterogeneity and asymmetry of the chromatin environment at regulatory elements Kundaje, A.; Kyriazopoulou-Panagiotopoulou, S.; Libbrecht, M. Genome Research, Vol. 22, Issue 9 https://doi.org/10.1101/gr.136366.111	journal	September 2012
Function-based identification of mammalian enhancers using site-specific integration Dickel, Diane E.; Zhu, Yiwen; Nord, Alex S. Nature Methods, Vol. 11, Issue 5 https://doi.org/10.1038/nmeth.2886	journal	March 2014
SCL and associated proteins distinguish active from repressive GATA transcription factor complexes Tripic, Tamara; Deng, Wulan; Cheng, Yong Blood, Vol. 113, Issue 10 https://doi.org/10.1182/blood-2008-07-169417	journal	March 2009
FIREWACh: high-throughput functional detection of transcriptional regulatory modules in mammalian cells Murtha, Matthew; Tokcaer-Keskin, Zeynep; Tang, Zuojian Nature Methods, Vol. 11, Issue 5 https://doi.org/10.1038/nmeth.2885	journal	March 2014
Integrative annotation of chromatin elements from ENCODE data Hoffman, Michael M.; Ernst, Jason; Wilder, Steven P. Nucleic Acids Research, Vol. 41, Issue 2 https://doi.org/10.1093/nar/gks1284	journal	December 2012
The Human Genome Browser at UCSC Kent, W. J. Genome Research, Vol. 12, Issue 6 https://doi.org/10.1101/gr.229102. Article published online before print in May 2002	journal	May 2002
Neurogenin Promotes Neurogenesis and Inhibits Glial Differentiation by Independent Mechanisms Sun, Yi; Nadal-Vicens, Mireya; Misono, Stephanie Cell, Vol. 104, Issue 3 https://doi.org/10.1016/S0092-8674(01)00224-0	journal	February 2001
Experimental validation of predicted mammalian erythroid cis-regulatory modules Wang, H.; Zhang, Y.; Cheng, Y. Genome Research, Vol. 16, Issue 12 https://doi.org/10.1101/gr.5353806	journal	October 2006
Transcriptional enhancement by GATA1-occupied DNA segments is strongly associated with evolutionary constraint on the binding site motif Cheng, Y.; King, D. C.; Dore, L. C. Genome Research, Vol. 18, Issue 12 https://doi.org/10.1101/gr.083089.108	journal	October 2008
Massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of ChIP-seq peaks White, M. A.; Myers, C. A.; Corbo, J. C. Proceedings of the National Academy of Sciences, Vol. 110, Issue 29 https://doi.org/10.1073/pnas.1307449110	journal	July 2013
Genomic approaches towards finding cis-regulatory modules in animals Hardison, Ross C.; Taylor, James Nature Reviews Genetics, Vol. 13, Issue 7 https://doi.org/10.1038/nrg3242	journal	June 2012
Genome-wide comparative analysis reveals human-mouse regulatory landscape and evolution Denas, Olgert; Sandstrom, Richard; Cheng, Yong BMC Genomics, Vol. 16, Issue 1 https://doi.org/10.1186/s12864-015-1245-6	journal	January 2015
The role of Tal2 and Tal1 in the differentiation of midbrain GABAergic neuron precursors Achim, K.; Peltopuro, P.; Lahti, L. Biology Open, Vol. 2, Issue 10 https://doi.org/10.1242/bio.20135041	journal	August 2013
Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells Attanasio, Catia; Reymond, Alexandre; Humbert, Richard Genome Biology, Vol. 9, Issue 12 https://doi.org/10.1186/gb-2008-9-12-r168	journal	January 2008
Hematopoiesis: An Evolving Paradigm for Stem Cell Biology Orkin, Stuart H.; Zon, Leonard I. Cell, Vol. 132, Issue 4 https://doi.org/10.1016/j.cell.2008.01.025	journal	February 2008
An integrated encyclopedia of DNA elements in the human genome Nature, Vol. 489, Issue 7414, p. 57-74 https://doi.org/10.1038/nature11247	journal	September 2012
Human beta-globin locus control region: analysis of the 5' DNase I hypersensitive site HS 2 in transgenic mice. Caterina, J. J.; Ryan, T. M.; Pawlik, K. M. Proceedings of the National Academy of Sciences, Vol. 88, Issue 5 https://doi.org/10.1073/pnas.88.5.1626	journal	March 1991
Histone modifications at human enhancers reflect global cell-type-specific gene expression Heintzman, Nathaniel D.; Hon, Gary C.; Hawkins, R. David Nature, Vol. 459, Issue 7243 https://doi.org/10.1038/nature07829	journal	March 2009
Minichromosome assembly of non-integrated plasmid DNA transfected into mammalian cells Reeves, Raymond; Gorman, Cornelia M.; Howard, Bruce Nucleic Acids Research, Vol. 13, Issue 10 https://doi.org/10.1093/nar/13.10.3599	journal	January 1985
Tissue-specific transcriptional regulation has diverged significantly between human and mouse Odom, Duncan T.; Dowell, Robin D.; Jacobsen, Elizabeth S. Nature Genetics, Vol. 39, Issue 6 https://doi.org/10.1038/ng2047	journal	May 2007
Haemogenic endocardium contributes to transient definitive haematopoiesis Nakano, Haruko; Liu, Xiaoqian; Arshi, Armin Nature Communications, Vol. 4, Issue 1 https://doi.org/10.1038/ncomms2569	journal	March 2013
A Runx1 Intronic Enhancer Marks Hemogenic Endothelial Cells and Hematopoietic Stem Cells Ng, Cherry Ee Lin; Yokomizo, Tomomasa; Yamashita, Namiko STEM CELLS, Vol. 28, Issue 10 https://doi.org/10.1002/stem.507	journal	October 2010
Embryonic-fetal erythroid characteristics of a human leukemic cell line. Benz, E. J.; Murnane, M. J.; Tonkonow, B. L. Proceedings of the National Academy of Sciences, Vol. 77, Issue 6 https://doi.org/10.1073/pnas.77.6.3509	journal	June 1980
BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources Wu, Chunlei; Orozco, Camilo; Boyer, Jason Genome Biology, Vol. 10, Issue 11 https://doi.org/10.1186/gb-2009-10-11-r130	journal	January 2009
Of lineage and legacy: the development of mammalian hematopoietic stem cells Dzierzak, Elaine; Speck, Nancy A. Nature Immunology, Vol. 9, Issue 2 https://doi.org/10.1038/ni1560	journal	January 2008
The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation Soler, E.; Andrieu-Soler, C.; de Boer, E. Genes & Development, Vol. 24, Issue 3 https://doi.org/10.1101/gad.551810	journal	February 2010
Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration Wu, W.; Cheng, Y.; Keller, C. A. Genome Research, Vol. 21, Issue 10 https://doi.org/10.1101/gr.125088.111	journal	July 2011
Primary sequence and epigenetic determinants of in vivo occupancy of genomic DNA by GATA1 Zhang, Ying; Wu, Weisheng; Cheng, Yong Nucleic Acids Research, Vol. 37, Issue 21 https://doi.org/10.1093/nar/gkp747	journal	September 2009
VISTA Enhancer Browser--a database of tissue-specific human enhancers Visel, A.; Minovitsky, S.; Dubchak, I. Nucleic Acids Research, Vol. 35, Issue Database https://doi.org/10.1093/nar/gkl822	journal	January 2007
NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers Wang, H.; Zang, C.; Taing, L. Proceedings of the National Academy of Sciences, Vol. 111, Issue 2 https://doi.org/10.1073/pnas.1315023111	journal	December 2013
The embryonic origins of erythropoiesis in mammals Baron, Margaret H.; Isern, Joan; Fraser, Stuart T. Blood, Vol. 119, Issue 21 https://doi.org/10.1182/blood-2012-01-153486	journal	May 2012
Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay Kheradpour, P.; Ernst, J.; Melnikov, A. Genome Research, Vol. 23, Issue 5 https://doi.org/10.1101/gr.144899.112	journal	March 2013
Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq Arnold, C. D.; Gerlach, D.; Stelzer, C. Science, Vol. 339, Issue 6123 https://doi.org/10.1126/science.1232542	journal	January 2013
Smad transcription factors Massague, J. Genes & Development, Vol. 19, Issue 23 https://doi.org/10.1101/gad.1350705	journal	December 2005
Sequence and chromatin determinants of cell-type-specific transcription factor binding Arvey, A.; Agius, P.; Noble, W. S. Genome Research, Vol. 22, Issue 9 https://doi.org/10.1101/gr.127712.111	journal	September 2012
The T Cell Leukemia Oncoprotein SCL/tal-1 Is Essential for Development of All Hematopoietic Lineages Porcher, Catherine; Swat, Wojciech; Rockwell, Karen Cell, Vol. 86, Issue 1 https://doi.org/10.1016/S0092-8674(00)80076-8	journal	July 1996
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence Org, Tõnis; Duan, Dan; Ferrari, Roberto The EMBO Journal, Vol. 34, Issue 6 https://doi.org/10.15252/embj.201490542	journal	December 2014
ChromHMM: automating chromatin-state discovery and characterization Ernst, Jason; Kellis, Manolis Nature Methods, Vol. 9, Issue 3 https://doi.org/10.1038/nmeth.1906	journal	February 2012
Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes Gorkin, D. U.; Lee, D.; Reed, X. Genome Research, Vol. 22, Issue 11 https://doi.org/10.1101/gr.139360.112	journal	September 2012
Epigenetic signatures distinguish multiple classes of enhancers with distinct cellular functions Zentner, Gabriel E.; Tesar, Paul J.; Scacheri, Peter C. Genome Research, Vol. 21, Issue 8 https://doi.org/10.1101/gr.122382.111	journal	June 2011
Nucleosome dynamics define transcriptional enhancers He, Housheng Hansen; Meyer, Clifford A.; Shin, Hyunjin Nature Genetics, Vol. 42, Issue 4 https://doi.org/10.1038/ng.545	journal	March 2010
CODEX: a next-generation sequencing experiment database for the haematopoietic and embryonic stem cell communities Sánchez-Castillo, Manuel; Ruau, David; Wilkinson, Adam C. Nucleic Acids Research, Vol. 43, Issue D1 https://doi.org/10.1093/nar/gku895	journal	September 2014
Genome-wide MyoD Binding in Skeletal Muscle Cells: A Potential for Broad Cellular Reprogramming Cao, Yi; Yao, Zizhen; Sarkar, Deepayan Developmental Cell, Vol. 18, Issue 4 https://doi.org/10.1016/j.devcel.2010.02.014	journal	April 2010
Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors Wang, J.; Zhuang, J.; Iyer, S. Genome Research, Vol. 22, Issue 9 https://doi.org/10.1101/gr.139105.112	journal	September 2012
Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model Smith, Robin P.; Taher, Leila; Patwardhan, Rupali P. Nature Genetics, Vol. 45, Issue 9 https://doi.org/10.1038/ng.2713	journal	July 2013
ESPERR: Learning strong and weak signals in genomic sequence alignments to identify functional elements Taylor, J.; Tyekucheva, S.; King, D. C. Genome Research, Vol. 16, Issue 12 https://doi.org/10.1101/gr.4537706	journal	October 2006
Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-β Signaling Mullen, Alan C.; Orlando, David A.; Newman, Jamie J. Cell, Vol. 147, Issue 3 https://doi.org/10.1016/j.cell.2011.08.050	journal	October 2011
Functions of BET proteins in erythroid gene expression Stonestrom, Aaron J.; Hsu, Sarah C.; Jahn, Kristen S. Blood, Vol. 125, Issue 18 https://doi.org/10.1182/blood-2014-10-607309	journal	April 2015
A Negative Cis-element Regulates the Level of Enhancement by Hypersensitive Site 2 of the β-Globin Locus Control Region Elnitski, Laura; Li, Jin; Noguchi, Constance Tom Journal of Biological Chemistry, Vol. 276, Issue 9 https://doi.org/10.1074/jbc.M009624200	journal	November 2000
Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)–dependent window during hematopoietic stem-cell development Schlaeger, Thorsten M.; Mikkola, Hanna K. A.; Gekas, Christos Blood, Vol. 105, Issue 10 https://doi.org/10.1182/blood-2004-11-4467	journal	May 2005
Transcriptional regulation by STAT1 and STAT2 in the interferon JAK-STAT pathway Au-Yeung, Nancy; Mandhana, Roli; Horvath, Curt M. JAK-STAT, Vol. 2, Issue 3 https://doi.org/10.4161/jkst.23931	journal	July 2013
ChIP-Seq identification of weakly conserved heart enhancers Blow, Matthew J.; McCulley, David J.; Li, Zirong Nature Genetics, Vol. 42, Issue 9 https://doi.org/10.1038/ng.650	journal	August 2010
CREB-binding Protein and p300 in Transcriptional Regulation Vo, Ngan; Goodman, Richard H. Journal of Biological Chemistry, Vol. 276, Issue 17 https://doi.org/10.1074/jbc.R000025200	journal	March 2001
Combinatorial Assembly of Developmental Stage-Specific Enhancers Controls Gene Expression Programs during Human Erythropoiesis Xu, Jian; Shao, Zhen; Glass, Kimberly Developmental Cell, Vol. 23, Issue 4 https://doi.org/10.1016/j.devcel.2012.09.003	journal	October 2012
Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells. Ney, P. A.; Sorrentino, B. P.; McDonagh, K. T. Genes & Development, Vol. 4, Issue 6 https://doi.org/10.1101/gad.4.6.993	journal	June 1990
Five-Vertebrate ChIP-seq Reveals the Evolutionary Dynamics of Transcription Factor Binding Schmidt, D.; Wilson, M. D.; Ballester, B. Science, Vol. 328, Issue 5981 https://doi.org/10.1126/science.1186176	journal	April 2010
Principles of regulatory information conservation between mouse and human Cheng, Yong; Ma, Zhihai; Kim, Bong-Hyun Nature, Vol. 515, Issue 7527 https://doi.org/10.1038/nature13985	journal	November 2014
ICOS Coreceptor Signaling Inactivates the Transcription Factor FOXO1 to Promote Tfh Cell Differentiation Stone, Erica L.; Pepper, Marion; Katayama, Carol D. Immunity, Vol. 42, Issue 2 https://doi.org/10.1016/j.immuni.2015.01.017	journal	February 2015
NEW EMBO MEMBERS REVIEW: Transcriptional control by the TGF-beta/Smad signaling system Massague, J. The EMBO Journal, Vol. 19, Issue 8 https://doi.org/10.1093/emboj/19.8.1745	journal	April 2000
Integration of Smad and Forkhead Pathways in the Control of Neuroepithelial and Glioblastoma Cell Proliferation Seoane, Joan; Le, Hong-Van; Shen, Lijian Cell, Vol. 117, Issue 2 https://doi.org/10.1016/S0092-8674(04)00298-3	journal	April 2004
Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay Melnikov, Alexandre; Murugan, Anand; Zhang, Xiaolan Nature Biotechnology, Vol. 30, Issue 3 https://doi.org/10.1038/nbt.2137	journal	February 2012
In vivo enhancer analysis of human conserved non-coding sequences Pennacchio, Len A.; Ahituv, Nadav; Moses, Alan M. Nature, Vol. 444, Issue 7118 https://doi.org/10.1038/nature05295	journal	November 2006
High-throughput functional testing of ENCODE segmentation predictions Kwasnieski, Jamie C.; Fiore, Christopher; Chaudhari, Hemangi G. Genome Research, Vol. 24, Issue 10 https://doi.org/10.1101/gr.173518.114	journal	July 2014
Quantifying similarity between motifs Gupta, Shobhit; Stamatoyannopoulos, John A.; Bailey, Timothy L. Genome Biology, Vol. 8, Issue 2 https://doi.org/10.1186/gb-2007-8-2-r24	journal	January 2007
Finding cis-regulatory elements using comparative genomics: Some lessons from ENCODE data King, D. C.; Taylor, J.; Zhang, Y. Genome Research, Vol. 17, Issue 6 https://doi.org/10.1101/gr.5592107	journal	June 2007
Turning cells red: signal transduction mediated by erythropoietin Richmond, Terri D.; Chohan, Manprit; Barber, Dwayne L. Trends in Cell Biology, Vol. 15, Issue 3 https://doi.org/10.1016/j.tcb.2005.01.007	journal	March 2005
Integrating Diverse Datasets Improves Developmental Enhancer Prediction Erwin, Genevieve D.; Oksenberg, Nir; Truty, Rebecca M. PLoS Computational Biology, Vol. 10, Issue 6 https://doi.org/10.1371/journal.pcbi.1003677	journal	June 2014
Conserved noncoding sequences are reliable guides to regulatory elements Hardison, R. Trends in Genetics, Vol. 16, Issue 9 https://doi.org/10.1016/S0168-9525(00)02081-3	journal	September 2000
An atlas of active enhancers across human cell types and tissues Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene Nature, Vol. 507, Issue 7493 https://doi.org/10.1038/nature12787	journal	March 2014
Genome accessibility is widely preserved and locally modulated during mitosis Hsiung, Chris C. -S.; Morrissey, Christapher S.; Udugama, Maheshi Genome Research, Vol. 25, Issue 2 https://doi.org/10.1101/gr.180646.114	journal	November 2014
A comparative encyclopedia of DNA elements in the mouse genome Yue, Feng; Cheng, Yong; Breschi, Alessandra Nature, Vol. 515, Issue 7527 https://doi.org/10.1038/nature13992	journal	November 2014
Identifying tissue-selective transcription factor binding sites in vertebrate promoters Smith, A. D.; Sumazin, P.; Zhang, M. Q. Proceedings of the National Academy of Sciences, Vol. 102, Issue 5 https://doi.org/10.1073/pnas.0406123102	journal	January 2005
Dynamic shifts in occupancy by TAL1 are guided by GATA factors and drive large-scale reprogramming of gene expression during hematopoiesis Wu, Weisheng; Morrissey, Christapher S.; Keller, Cheryl A. Genome Research, Vol. 24, Issue 12 https://doi.org/10.1101/gr.164830.113	journal	October 2014
GATA-1 and Erythropoietin Cooperate to Promote Erythroid Cell Survival by Regulating bcl-xL Expression Gregory, Todd; Yu, Channing; Ma, Averil Blood, Vol. 94, Issue 1 https://doi.org/10.1182/blood.V94.1.87.413k41_87_96	journal	July 1999
The Human Genome Browser at UCSC Kent, W. J. Genome Research, Vol. 12, Issue 6 https://doi.org/10.1101/gr.229102.	journal	May 2002
Distribution and storage of inflammatory memory in barrier tissues Ordovas-Montanes, Jose; Beyaz, Semir; Rakoff-Nahoum, Seth Nature Reviews Immunology, Vol. 20, Issue 5 https://doi.org/10.1038/s41577-019-0263-z	journal	February 2020
Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration A., Blobel, G.; F., Chiaromonte,; C., Morrissey, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/cyd4-7z83	text	January 2011
Nucleosome dynamics define transcriptional enhancers Keji, Zhao,; Mathieu, Lupien,; Kexin, Xu, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/4sp1-g908	text	January 2010
JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles Michelle, Zhou,; Ge, Tan,; Hans, Ienasescu, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/gepd-y994	text	January 2014
An integrated encyclopedia of DNA elements in the human genome Libraries, The University of North Carolina at Chapel Hill University The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/wcvb-k036	text	January 2012
Lineage Regulators Direct BMP and Wnt Pathways to Cell-Specific Programs During Differentiation and Regeneration, Bowman, Teresa V.; Trompouki, Eirini; Lawton, Lee N. Blood, Vol. 118, Issue 21 https://doi.org/10.1182/blood.v118.21.3387.3387	journal	November 2011
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project K., Clelland, Gayle; M., Taylor, Christopher; Saurabh, Asthana, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/d7n3-p041	text	January 2007
Single-nuclei isoform RNA sequencing unlocks barcoded exon connectivity in frozen brain tissue Hardwick, Simon A.; Hu, Wen; Joglekar, Anoushka Nature Biotechnology, Vol. 40, Issue 7 https://doi.org/10.1038/s41587-022-01231-3	journal	March 2022
The Human Genome Browser at UCSC Kent, W. J.; Sugnet, C. W.; Furey, T. S. Genome Research, Vol. 12, Issue 6 https://doi.org/10.1101/gr.229102	journal	May 2002
cis-Regulatory Remodeling of the SCL Locus during Vertebrate Evolution Gottgens, B.; Ferreira, R.; Sanchez, M. -J. Molecular and Cellular Biology, Vol. 30, Issue 24 https://doi.org/10.1128/mcb.00870-10	journal	October 2010
Molecular Hallmarks of Endogenous Chromatin Complexes Containing Master Regulators of Hematopoiesis Wozniak, R. J.; Keles, S.; Lugus, J. J. Molecular and Cellular Biology, Vol. 28, Issue 21 https://doi.org/10.1128/mcb.01061-08	journal	September 2008
Erythroid-cell-specific properties of transcription factor GATA-1 revealed by phenotypic rescue of a gene-targeted cell line. Weiss, M. J.; Yu, C.; Orkin, S. H. Molecular and Cellular Biology, Vol. 17, Issue 3 https://doi.org/10.1128/mcb.17.3.1642	journal	March 1997
mSin3A Regulates Murine Erythroleukemia Cell Differentiation through Association with the TAL1 (or SCL) Transcription Factor Huang, S.; Brandt, S. J. Molecular and Cellular Biology, Vol. 20, Issue 6 https://doi.org/10.1128/mcb.20.6.2248-2259.2000	journal	March 2000
Transcriptional Regulation of Cardiac Progenitor Cell Populations Masino, Amanda M.; Gallardo, Teresa D.; Wilcox, Celeste A. Circulation Research, Vol. 95, Issue 4 https://doi.org/10.1161/01.res.0000138302.02691.be	journal	August 2004
Take Heart in the Age of “Omics” Abu-Issa, Radwan; Kirby, Margaret L. Circulation Research, Vol. 95, Issue 4 https://doi.org/10.1161/01.res.0000141017.99175.dd	journal	August 2004
Foxo3 is required for the regulation of oxidative stress in erythropoiesis Marinkovic, Dragan; Zhang, Xin; Yalcin, Safak Journal of Clinical Investigation, Vol. 117, Issue 8 https://doi.org/10.1172/jci31807	journal	August 2007
Identification of the human erythropoietin receptor region required for Stat1 and Stat3 activation Kirito, Keita; Nakajima, Koichi; Watanabe, Tomoko Blood, Vol. 99, Issue 1 https://doi.org/10.1182/blood.v99.1.102	journal	January 2002
Creating cellular diversity through transcription factor competition Göttgens, Berthold The EMBO Journal, Vol. 34, Issue 6 https://doi.org/10.15252/embj.201591017	journal	February 2015
Integrating diverse datasets improves developmental enhancer prediction Erwin, Genevieve D.; Truty, Rebecca M.; Kostka, Dennis arXiv https://doi.org/10.48550/arxiv.1309.7382	text	January 2013

Cited By (37)

Multiple enhancer regions govern the transcription of CCN2 during embryonic development Frost, Stephanie L.; Liu, Ke; Li, Ian M. H. Journal of Cell Communication and Signaling, Vol. 12, Issue 1 https://doi.org/10.1007/s12079-017-0440-4	journal	December 2017
Repurposing of promoters and enhancers during mammalian evolution Carelli, Francesco N.; Liechti, Angélica; Halbert, Jean Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-06544-z	journal	October 2018
C/EBPβ regulates Vegf gene expression in granulosa cells undergoing luteinization during ovulation in female rats Shinagawa, Masahiro; Tamura, Isao; Maekawa, Ryo Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-018-36566-y	journal	January 2019
DNA demethylation facilitates the specific transcription of the mouse X-linked Tsga8 gene in round spermatids† Lu, Yongjie; Liao, Shunyao; Tu, Wenling Biology of Reproduction, Vol. 100, Issue 4 https://doi.org/10.1093/biolre/ioy255	journal	December 2018
Towards a map of cis-regulatory sequences in the human genome Niu, Meng; Tabari, Ehsan; Ni, Pengyu Nucleic Acids Research, Vol. 46, Issue 11 https://doi.org/10.1093/nar/gky338	journal	May 2018
An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis Xiang, Guanjue; Keller, Cheryl A.; Heuston, Elisabeth bioRxiv https://doi.org/10.1101/731729	posted_content	January 2020
Enhancer prediction in the human genome by probabilistic modeling of the chromatin feature patterns Osmala, Maria; Lähdesmäki, Harri BMC Bioinformatics https://doi.org/10.1101/804625	posted_content	June 2020
Total Functional Score of Enhancer Elements Identifies Lineage-Specific Enhancers That Drive Differentiation of Pancreatic Cells Malladi, Venkat S.; Nagari, Anusha; Franco, Hector L. Bioinformatics and Biology Insights, Vol. 14 https://doi.org/10.1177/1177932220938063	journal	January 2020
Blood disease–causing and –suppressing transcriptional enhancers: general principles and GATA2 mechanisms Bresnick, Emery H.; Johnson, Kirby D. Blood Advances, Vol. 3, Issue 13 https://doi.org/10.1182/bloodadvances.2019000378	journal	July 2019
Properties of STAT1 and IRF1 enhancers and the influence of SNPs Abou El Hassan, Mohamed; Huang, Katherine; Eswara, Manoja B. K. BMC Molecular Biology, Vol. 18, Issue 1 https://doi.org/10.1186/s12867-017-0084-1	journal	March 2017
Establishment of regulatory elements during erythro-megakaryopoiesis identifies hematopoietic lineage-commitment points Heuston, Elisabeth F.; Keller, Cheryl A.; Lichtenberg, Jens Epigenetics & Chromatin, Vol. 11, Issue 1 https://doi.org/10.1186/s13072-018-0195-z	journal	May 2018
Recent advances in high-throughput approaches to dissect enhancer function Santiago-Algarra, David; Dao, Lan T. M.; Pradel, Lydie F1000Research, Vol. 6 https://doi.org/10.12688/f1000research.11581.1	journal	January 2017
Limb-Enhancer Genie: An accessible resource of accurate enhancer predictions in the developing limb Monti, Remo; Barozzi, Iros; Osterwalder, Marco PLOS Computational Biology, Vol. 13, Issue 8 https://doi.org/10.1371/journal.pcbi.1005720	journal	August 2017
Systematic integration of GATA transcription factors and epigenomes via IDEAS paints the regulatory landscape of hematopoietic cells Hardison, Ross C.; Zhang, Yu; Keller, Cheryl A. IUBMB Life, Vol. 72, Issue 1 https://doi.org/10.1002/iub.2195	journal	November 2019
BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis Canver, Matthew C.; Smith, Elenoe C.; Sher, Falak Nature, Vol. 527, Issue 7577 https://doi.org/10.1038/nature15521	journal	September 2015
Chromatin accessibility and the regulatory epigenome Klemm, Sandy L.; Shipony, Zohar; Greenleaf, William J. Nature Reviews Genetics, Vol. 20, Issue 4 https://doi.org/10.1038/s41576-018-0089-8	journal	January 2019
Chromatin structure dynamics during the mitosis-to-G1 phase transition Zhang, Haoyue; Emerson, Daniel J.; Gilgenast, Thomas G. Nature, Vol. 576, Issue 7785 https://doi.org/10.1038/s41586-019-1778-y	journal	November 2019
Exploiting regulatory heterogeneity to systematically identify enhancers with high accuracy Arbel, Hamutal; Basu, Sumanta; Fisher, William W. Proceedings of the National Academy of Sciences, Vol. 116, Issue 3 https://doi.org/10.1073/pnas.1808833115	journal	December 2018
Systematic integration of GATA transcription factors and epigenomes via IDEAS paints the regulatory landscape of mouse hematopoietic cells Hardison, Ross C.; Zhang, Yu; Keller, Cheryl A. IUBMB Life https://doi.org/10.1101/730358	posted_content	August 2019
A hyperactive transcriptional state marks genome reactivation at the mitosis–G1 transition Hsiung, Chris C. -S.; Bartman, Caroline R.; Huang, Peng Genes & Development, Vol. 30, Issue 12 https://doi.org/10.1101/gad.280859.116	journal	June 2016
Genome-wide enhancer annotations differ significantly in genomic distribution, evolution, and function Benton, Mary Lauren; Talipineni, Sai Charan; Kostka, Dennis BMC Genomics, Vol. 20, Issue 1 https://doi.org/10.1186/s12864-019-5779-x	journal	June 2019
Beyond the Exome: The Non-coding Genome and Enhancers in Neurodevelopmental Disorders and Malformations of Cortical Development Perenthaler, Elena; Yousefi, Soheil; Niggl, Eva Frontiers in Cellular Neuroscience, Vol. 13 https://doi.org/10.3389/fncel.2019.00352	journal	July 2019
The Conserved Non-Coding Sequence 2 (CNS2) Enhances CD69 Transcription through Cooperation between the Transcription Factors Oct1 and RUNX1 Fontela, Miguel G.; Notario, Laura; Alari-Pahissa, Elisenda Genes, Vol. 10, Issue 9 https://doi.org/10.3390/genes10090651	journal	August 2019
GATA factor transcriptional activity: Insights from genome‐wide binding profiles Romano, Oriana; Miccio, Annarita IUBMB Life, Vol. 72, Issue 1 https://doi.org/10.1002/iub.2169	journal	October 2019
A hyperactive transcriptional state marks genome reactivation at the mitosis-G1 transition Hsiung, Chris C. -S.; Bartman, Caroline; Huang, Peng Genes & Development https://doi.org/10.1101/053678	posted_content	May 2016
Enhancer transcription identifies cis-regulatory elements for photoreceptor cell types Nadadur, Rangarajan D.; Perez-Cervantes, Carlos; Lonfat, Nicolas bioRxiv https://doi.org/10.1101/513598	posted_content	January 2019
An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis Xiang, Guanjue; Keller, Cheryl A.; Heuston, Elisabeth Genome Research, Vol. 30, Issue 3 https://doi.org/10.1101/gr.255760.119	journal	March 2020
Enhancer prediction in the human genome by probabilistic modelling of the chromatin feature patterns Osmala, Maria; Lähdesmäki, Harri BMC Bioinformatics, Vol. 21, Issue 1 https://doi.org/10.1186/s12859-020-03621-3	journal	July 2020
Limb-Enhancer Genie: An accessible resource of accurate enhancer predictions in the developing limb Monti, Remo; Barozzi, Iros; Osterwalder, Marco ETH Zurich https://doi.org/10.3929/ethz-b-000191745	text	January 2017
Enhancer transcription identifies cis -regulatory elements for photoreceptor cell types Perez-Cervantes, Carlos; Smith, Linsin A.; Nadadur, Rangarajan D. Development https://doi.org/10.1242/dev.184432	journal	January 2020
An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis. Xiang, Guanjue; Keller, Cheryl A.; Heuston, Elisabeth Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.50079	text	January 2020
Concise Review: Epigenetic Regulation of Hematopoiesis: Biological Insights and Therapeutic Applications Antoniani, Chiara; Romano, Oriana; Miccio, Annarita Stem Cells Translational Medicine, Vol. 6, Issue 12 https://doi.org/10.1002/sctm.17-0192	journal	October 2017
The proto-oncogenic protein TAL1 controls TGF-β1 signaling through interaction with SMAD3 Terme, Jean-Michel; Lemaire, Sébastien; Auboeuf, Didier Biochimie Open, Vol. 2 https://doi.org/10.1016/j.biopen.2016.05.001	journal	June 2016
Conserved Noncoding Elements in the Most Distant Genera of Cephalochordates: The Goldilocks Principle Yue, Jia-Xing; Kozmikova, Iryna; Ono, Hiroki Genome Biology and Evolution, Vol. 8, Issue 8 https://doi.org/10.1093/gbe/evw158	journal	July 2016
Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets. Vijayabaskar, Ms; Goode, Debbie K.; Obier, Nadine Public Library of Science (PLoS) https://doi.org/10.17863/cam.43329	journalarticle	January 2019
Spatiotemporal regulation of enhancers during cardiogenesis Dupays, Laurent; Mohun, Timothy The Francis Crick Institute https://doi.org/10.25418/crick.15180018	text	January 2021
Mapping cell type-specific transcriptional enhancers using high affinity, lineage-specific Ep300 bioChIP-seq Zhou, Pingzhu; Gu, Fei; Zhang, Lina eLife, Vol. 6 https://doi.org/10.7554/elife.22039	journal	January 2017

Similar Records

Integrative epigenomic analysis reveals unique epigenetic signatures involved in unipotency of mouse female germline stem cells

Journal Article · Wed Jul 27 00:00:00 EDT 2016 · Genome Biology (Online) · OSTI ID:1190586

Zhang, Xiao-Li; Wu, Jun; Wang, Jian; +10 more

The landscape of Chlamydomonas histone H3 lysine 4 methylation reveals both constant features and dynamic changes during the diurnal cycle

Journal Article · Fri Aug 19 00:00:00 EDT 2022 · The Plant Journal · OSTI ID:1190586

Strenkert, Daniela; Yildirim, Asli; Yan, Juying; +5 more

Identification of functional elements and regulatory circuits by Drosophila modENCODE

Journal Article · Wed Dec 22 00:00:00 EST 2010 · Science · OSTI ID:1190586

Roy, Sushmita; Ernst, Jason; Kharchenko, Peter V; +93 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
functional genomics
gene regulation
TAL1
GATA1
histone modifications
enhancer assay

Title: Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility

Citation Formats

References (116)

Cited By (37)

Similar Records

Related Subjects