Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers

Hashimoto, Hisayuki; Wang, Zhaoning; Garry, Glynnis A.; Malladi, Venkat S.; Botten, Giovanni A.; Ye, Wenduo; Zhou, Huanyu; Osterwalder, Marco; Dickel, Diane E.; Visel, Axel; Liu, Ning; Bassel-Duby, Rhonda; Olson, Eric N.

doi:10.1016/j.stem.2019.03.022

Title: Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers

Journal Article · Thu May 09 00:00:00 EDT 2019 · Cell Stem Cell

DOI:https://doi.org/10.1016/j.stem.2019.03.022· OSTI ID:1650065

Hashimoto, Hisayuki ^[1]; Wang, Zhaoning ^[1]; Garry, Glynnis A. ^[1]; Malladi, Venkat S. ^[1]; Botten, Giovanni A. ^[1]; Ye, Wenduo ^[1]; Zhou, Huanyu ^[1]; Osterwalder, Marco ^[2]; Dickel, Diane E. ^[2]; Visel, Axel ^[3]; Liu, Ning ^[1]; Bassel-Duby, Rhonda ^[1]; Olson, Eric N. ^[1]

Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Univ. of California, Merced, CA (United States)

The cardiogenic transcription factors (TFs) Mef2c, Gata4, and Tbx5 can directly reprogram fibroblasts to induced cardiac-like myocytes (iCLMs), presenting a potential source of cells for cardiac repair. While activity of these TFs is enhanced by Hand2 and Akt1, their genomic targets and interactions during reprogramming are not well studied. We performed genome-wide analyses of cardiogenic TF binding and enhancer profiling during cardiac reprogramming. We found that these TFs synergistically activate enhancers highlighted by Mef2c binding sites and that Hand2 and Akt1 coordinately recruit other TFs to enhancer elements. Intriguingly, these enhancer landscapes collectively resemble patterns of enhancer activation during embryonic cardiogenesis. We further constructed a cardiac reprogramming gene regulatory network and found repression of EGFR signaling pathway genes. Consistently, chemical inhibition of EGFR signaling augmented reprogramming. Thus, by defining epigenetic landscapes these findings reveal synergistic transcriptional activation across a broad landscape of cardiac enhancers and key signaling pathways that govern iCLM reprogramming.

View Accepted Manuscript (DOE)

Cite

Export

Save

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

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1650065

Journal Information:: Cell Stem Cell, Vol. 25, Issue 1; ISSN 1875-9777

Publisher:: Cell PressCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 45 works

Citation information provided by
Web of Science

References (78)

Epigenetics and Cardiovascular Development Chang, Ching-Pin; Bruneau, Benoit G. Annual Review of Physiology, Vol. 74, Issue 1 https://doi.org/10.1146/annurev-physiol-020911-153242	journal	March 2012
Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling Cohn, Jay N.; Ferrari, Roberto; Sharpe, Norman Journal of the American College of Cardiology, Vol. 35, Issue 3 https://doi.org/10.1016/S0735-1097(99)00630-0	journal	March 2000
Therapeutic approaches for cardiac regeneration and repair Hashimoto, Hisayuki; Olson, Eric N.; Bassel-Duby, Rhonda Nature Reviews Cardiology, Vol. 15, Issue 10 https://doi.org/10.1038/s41569-018-0036-6	journal	June 2018
Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors Ieda, Masaki; Fu, Ji-Dong; Delgado-Olguin, Paul Cell, Vol. 142, Issue 3 https://doi.org/10.1016/j.cell.2010.07.002	journal	August 2010
MiR‐133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures Muraoka, Naoto; Yamakawa, Hiroyuki; Miyamoto, Kazutaka The EMBO Journal, Vol. 33, Issue 14 https://doi.org/10.15252/embj.201387605	journal	June 2014
ErbB Receptor Tyrosine Kinase: A Molecular Switch Between Cardiac and Neuroectoderm Specification in Human Pluripotent Stem Cells: ErbB RTKs Regulate Cardio- and Neurogenesis Ramachandra, Chrishan J. A.; Mehta, Ashish; Lua, Chong Hui STEM CELLS, Vol. 34, Issue 10 https://doi.org/10.1002/stem.2420	journal	June 2016
Gene Regulatory Networks in the Evolution and Development of the Heart Olson, E. N. Science, Vol. 313, Issue 5795 https://doi.org/10.1126/science.1132292	journal	September 2006
Cardiac Regeneration: Lessons From Development Galdos, Francisco X.; Guo, Yuxuan; Paige, Sharon L. Circulation Research, Vol. 120, Issue 6 https://doi.org/10.1161/CIRCRESAHA.116.309040	journal	March 2017
Interaction of Gata4 and Gata6 with Tbx5 is critical for normal cardiac development Maitra, Meenakshi; Schluterman, Marie K.; Nichols, Haley A. Developmental Biology, Vol. 326, Issue 2 https://doi.org/10.1016/j.ydbio.2008.11.004	journal	February 2009
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
Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015 Roth, Gregory A.; Johnson, Catherine; Abajobir, Amanuel Journal of the American College of Cardiology, Vol. 70, Issue 1 https://doi.org/10.1016/j.jacc.2017.04.052	journal	July 2017
Fast and accurate short read alignment with Burrows-Wheeler transform Li, H.; Durbin, R. Bioinformatics, Vol. 25, Issue 14 https://doi.org/10.1093/bioinformatics/btp324	journal	May 2009
The Transcription Factors GATA4 and dHAND Physically Interact to Synergistically Activate Cardiac Gene Expression through a p300-dependent Mechanism Dai, Yan-Shan; Cserjesi, Peter; Markham, Bruce E. Journal of Biological Chemistry, Vol. 277, Issue 27 https://doi.org/10.1074/jbc.M202490200	journal	July 2002
Epidermal growth factor receptor (EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer (NSCLC) Kobayashi, Kunihiko; Hagiwara, Koichi Targeted Oncology, Vol. 8, Issue 1 https://doi.org/10.1007/s11523-013-0258-9	journal	January 2013
White-to-brown metabolic conversion of human adipocytes by JAK inhibition Moisan, Annie; Lee, Youn-Kyoung; Zhang, Jitao David Nature Cell Biology, Vol. 17, Issue 1 https://doi.org/10.1038/ncb3075	journal	December 2014
Design and analysis of ChIP-seq experiments for DNA-binding proteins Kharchenko, Peter V.; Tolstorukov, Michael Y.; Park, Peter J. Nature Biotechnology, Vol. 26, Issue 12 https://doi.org/10.1038/nbt.1508	journal	November 2008
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters Yu, Guangchuang; Wang, Li-Gen; Han, Yanyan OMICS: A Journal of Integrative Biology, Vol. 16, Issue 5 https://doi.org/10.1089/omi.2011.0118	journal	May 2012
Disease Model of GATA4 Mutation Reveals Transcription Factor Cooperativity in Human Cardiogenesis Ang, Yen-Sin; Rivas, Renee N.; Ribeiro, Alexandre J. S. Cell, Vol. 167, Issue 7 https://doi.org/10.1016/j.cell.2016.11.033	journal	December 2016
HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development Laurent, Frédéric; Girdziusaite, Ausra; Gamart, Julie Cell Reports, Vol. 19, Issue 8 https://doi.org/10.1016/j.celrep.2017.05.004	journal	May 2017
Single-cell transcriptomics reconstructs fate conversion from fibroblast to cardiomyocyte Liu, Ziqing; Wang, Li; Welch, Joshua D. Nature, Vol. 551, Issue 7678 https://doi.org/10.1038/nature24454	journal	October 2017
PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements Mi, Huaiyu; Huang, Xiaosong; Muruganujan, Anushya Nucleic Acids Research, Vol. 45, Issue D1 https://doi.org/10.1093/nar/gkw1138	journal	November 2016
Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors Lalit, Pratik A.; Salick, Max R.; Nelson, Daryl O. Cell Stem Cell, Vol. 18, Issue 3 https://doi.org/10.1016/j.stem.2015.12.001	journal	March 2016
Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage Wamstad, Joseph A.; Alexander, Jeffrey M.; Truty, Rebecca M. Cell, Vol. 151, Issue 1 https://doi.org/10.1016/j.cell.2012.07.035	journal	September 2012
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
Induction of human cardiomyocyte-like cells from fibroblasts by defined factors Wada, R.; Muraoka, N.; Inagawa, K. Proceedings of the National Academy of Sciences, Vol. 110, Issue 31 https://doi.org/10.1073/pnas.1304053110	journal	July 2013
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features Liao, Y.; Smyth, G. K.; Shi, W. Bioinformatics, Vol. 30, Issue 7 https://doi.org/10.1093/bioinformatics/btt656	journal	November 2013
Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells King, Andrew D.; Huang, Kevin; Rubbi, Liudmilla Cell Reports, Vol. 17, Issue 1 https://doi.org/10.1016/j.celrep.2016.08.083	journal	September 2016
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
Induction of diverse cardiac cell types by reprogramming fibroblasts with cardiac transcription factors Nam, Young-Jae; Lubczyk, Christina; Bhakta, Minoti Development, Vol. 141, Issue 22 https://doi.org/10.1242/dev.114025	journal	November 2014
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
Altered Right Atrial Excitation and Propagation in Connexin40 Knockout Mice Bagwe, Suveer; Berenfeld, Omer; Vaidya, Dhananjay Circulation, Vol. 112, Issue 15 https://doi.org/10.1161/CIRCULATIONAHA.104.527325	journal	October 2005
Small Molecules Enable Cardiac Reprogramming of Mouse Fibroblasts with a Single Factor, Oct4 Wang, Haixia; Cao, Nan; Spencer, C. Ian Cell Reports, Vol. 6, Issue 5 https://doi.org/10.1016/j.celrep.2014.01.038	journal	March 2014
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A. Nature Protocols, Vol. 4, Issue 1 https://doi.org/10.1038/nprot.2008.211	journal	December 2008
Direct reprogramming of mouse fibroblasts into cardiomyocytes with chemical cocktails Fu, Yanbin; Huang, Chenwen; Xu, Xinxiu Cell Research, Vol. 25, Issue 9 https://doi.org/10.1038/cr.2015.99	journal	August 2015
Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors Takahashi, Kazutoshi; Yamanaka, Shinya Cell, Vol. 126, Issue 4 https://doi.org/10.1016/j.cell.2006.07.024	journal	August 2006
GATA-dependent recruitment of MEF2 proteins to target promoters Morin, S. The EMBO Journal, Vol. 19, Issue 9 https://doi.org/10.1093/emboj/19.9.2046	journal	May 2000
High-efficiency reprogramming of fibroblasts into cardiomyocytes requires suppression of pro-fibrotic signalling Zhao, Yuanbiao; Londono, Pilar; Cao, Yingqiong Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms9243	journal	September 2015
Notch Inhibition Enhances Cardiac Reprogramming by Increasing MEF2C Transcriptional Activity Abad, Maria; Hashimoto, Hisayuki; Zhou, Huanyu Stem Cell Reports, Vol. 8, Issue 3 https://doi.org/10.1016/j.stemcr.2017.01.025	journal	March 2017
Identifying ChIP-seq enrichment using MACS Feng, Jianxing; Liu, Tao; Qin, Bo Nature Protocols, Vol. 7, Issue 9 https://doi.org/10.1038/nprot.2012.101	journal	August 2012
Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo Gilsbach, Ralf; Schwaderer, Martin; Preissl, Sebastian Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-017-02762-z	journal	January 2018
Direct Reprogramming of Human Fibroblasts toward a Cardiomyocyte-like State Fu, Ji-Dong; Stone, Nicole R.; Liu, Lei Stem Cell Reports, Vol. 1, Issue 3 https://doi.org/10.1016/j.stemcr.2013.07.005	journal	September 2013
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
Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis Luna-Zurita, Luis; Stirnimann, Christian U.; Glatt, Sebastian Cell, Vol. 164, Issue 5 https://doi.org/10.1016/j.cell.2016.01.004	journal	February 2016
deepTools2: a next generation web server for deep-sequencing data analysis Ramírez, Fidel; Ryan, Devon P.; Grüning, Björn Nucleic Acids Research, Vol. 44, Issue W1 https://doi.org/10.1093/nar/gkw257	journal	April 2016
Transcription factors: from enhancer binding to developmental control Spitz, François; Furlong, Eileen E. M. Nature Reviews Genetics, Vol. 13, Issue 9 https://doi.org/10.1038/nrg3207	journal	August 2012
Patterning the vertebrate heart Harvey, Richard P. Nature Reviews Genetics, Vol. 3, Issue 7 https://doi.org/10.1038/nrg843	journal	July 2002
Reprogramming of human fibroblasts toward a cardiac fate Nam, Y. -J.; Song, K.; Luo, X. Proceedings of the National Academy of Sciences, Vol. 110, Issue 14 https://doi.org/10.1073/pnas.1301019110	journal	March 2013
The selection and function of cell type-specific enhancers Heinz, Sven; Romanoski, Casey E.; Benner, Christopher Nature Reviews Molecular Cell Biology, Vol. 16, Issue 3 https://doi.org/10.1038/nrm3949	journal	February 2015
Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice Condorelli, G.; Drusco, A.; Stassi, G. Proceedings of the National Academy of Sciences, Vol. 99, Issue 19 https://doi.org/10.1073/pnas.172376399	journal	September 2002
Glycogen Synthase Kinase 3β Regulates GATA4 in Cardiac Myocytes Morisco, Carmine; Seta, Koichi; Hardt, Stefan E. Journal of Biological Chemistry, Vol. 276, Issue 30 https://doi.org/10.1074/jbc.M103166200	journal	July 2001
Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart He, A.; Kong, S. W.; Ma, Q. Proceedings of the National Academy of Sciences, Vol. 108, Issue 14 https://doi.org/10.1073/pnas.1016959108	journal	March 2011
MicroRNA-Mediated In Vitro and In Vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes Jayawardena, Tilanthi M.; Egemnazarov, Bakytbek; Finch, Elizabeth A. Circulation Research, Vol. 110, Issue 11 https://doi.org/10.1161/CIRCRESAHA.112.269035	journal	May 2012
BEDTools: a flexible suite of utilities for comparing genomic features Quinlan, Aaron R.; Hall, Ira M. Bioinformatics, Vol. 26, Issue 6 https://doi.org/10.1093/bioinformatics/btq033	journal	January 2010
ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression Zhou, Huanyu; Morales, Maria Gabriela; Hashimoto, Hisayuki Genes & Development, Vol. 31, Issue 17 https://doi.org/10.1101/gad.305482.117	journal	September 2017
Chemical Enhancement of In Vitro and In Vivo Direct Cardiac Reprogramming Mohamed, Tamer M. A.; Stone, Nicole R.; Berry, Emily C. Circulation, Vol. 135, Issue 10 https://doi.org/10.1161/CIRCULATIONAHA.116.024692	journal	March 2017
Sambamba: fast processing of NGS alignment formats Tarasov, Artem; Vilella, Albert J.; Cuppen, Edwin Bioinformatics, Vol. 31, Issue 12 https://doi.org/10.1093/bioinformatics/btv098	journal	February 2015
MCAT Elements and the TEF-1 Family of Transcription Factors in Muscle Development and Disease Yoshida, Tadashi Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 28, Issue 1 https://doi.org/10.1161/ATVBAHA.107.155788	journal	January 2008
Structure and expression of the human slow twitch skeletal muscle troponin I gene. Corin, S. J.; Juhasz, O.; Zhu, L. Journal of Biological Chemistry, Vol. 269, Issue 14 https://doi.org/10.1016/S0021-9258(17)34109-1	journal	April 1994
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
Fibroblast Growth Factors and Vascular Endothelial Growth Factor Promote Cardiac Reprogramming under Defined Conditions Yamakawa, Hiroyuki; Muraoka, Naoto; Miyamoto, Kazutaka Stem Cell Reports, Vol. 5, Issue 6 https://doi.org/10.1016/j.stemcr.2015.10.019	journal	December 2015
Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A. Nucleic Acids Research, Vol. 37, Issue 1 https://doi.org/10.1093/nar/gkn923	journal	November 2008
An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133 Liu, N.; Williams, A. H.; Kim, Y. Proceedings of the National Academy of Sciences, Vol. 104, Issue 52 https://doi.org/10.1073/pnas.0710558105	journal	December 2007
Heart repair by reprogramming non-myocytes with cardiac transcription factors Song, Kunhua; Nam, Young-Jae; Luo, Xiang Nature, Vol. 485, Issue 7400 https://doi.org/10.1038/nature11139	journal	May 2012
The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field Jahangiri, Leila; Sharpe, Michka; Novikov, Natasha Development, Vol. 143, Issue 1 https://doi.org/10.1242/dev.126136	journal	January 2016
Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown Pertea, Mihaela; Kim, Daehwan; Pertea, Geo M. Nature Protocols, Vol. 11, Issue 9 https://doi.org/10.1038/nprot.2016.095	journal	August 2016
Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success Addis, Russell C.; Ifkovits, Jamie L.; Pinto, Filipa Journal of Molecular and Cellular Cardiology, Vol. 60 https://doi.org/10.1016/j.yjmcc.2013.04.004	journal	July 2013
MED12 Controls the Response to Multiple Cancer Drugs through Regulation of TGF-β Receptor Signaling Huang, Sidong; Hölzel, Michael; Knijnenburg, Theo Cell, Vol. 151, Issue 5 https://doi.org/10.1016/j.cell.2012.10.035	journal	November 2012
Genome-wide compendium and functional assessment of in vivo heart enhancers Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms12923	journal	October 2016
Ruxolitinib versus Standard Therapy for the Treatment of Polycythemia Vera Vannucchi, Alessandro M.; Kiladjian, Jean Jacques; Griesshammer, Martin New England Journal of Medicine, Vol. 372, Issue 5 https://doi.org/10.1056/NEJMoa1409002	journal	January 2015
Akt1/protein kinase B enhances transcriptional reprogramming of fibroblasts to functional cardiomyocytes Zhou, Huanyu; Dickson, Matthew E.; Kim, Min Soo Proceedings of the National Academy of Sciences, Vol. 112, Issue 38 https://doi.org/10.1073/pnas.1516237112	journal	September 2015
Stoichiometry of Gata4, Mef2c, and Tbx5 Influences the Efficiency and Quality of Induced Cardiac Myocyte Reprogramming Wang, Li; Liu, Ziqing; Yin, Chaoying Circulation Research, Vol. 116, Issue 2 https://doi.org/10.1161/CIRCRESAHA.116.305547	journal	January 2015
Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities Heinz, Sven; Benner, Christopher; Spann, Nathanael Molecular Cell, Vol. 38, Issue 4 https://doi.org/10.1016/j.molcel.2010.05.004	journal	May 2010
The Sequence Alignment/Map format and SAMtools Li, H.; Handsaker, B.; Wysoker, A. Bioinformatics, Vol. 25, Issue 16 https://doi.org/10.1093/bioinformatics/btp352	journal	June 2009
ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia Landt, S. G.; Marinov, G. K.; Kundaje, A. Genome Research, Vol. 22, Issue 9 https://doi.org/10.1101/gr.136184.111	journal	September 2012
Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis Huang, Jialiang; Liu, Xin; Li, Dan Developmental Cell, Vol. 36, Issue 1 https://doi.org/10.1016/j.devcel.2015.12.014	journal	January 2016
Creating reference gene annotation for the mouse C57BL6/J genome assembly Mudge, Jonathan M.; Harrow, Jennifer Mammalian Genome, Vol. 26, Issue 9-10 https://doi.org/10.1007/s00335-015-9583-x	journal	July 2015
Transcription Factors MYOCD, SRF, Mesp1 and SMARCD3 Enhance the Cardio-Inducing Effect of GATA4, TBX5, and MEF2C during Direct Cellular Reprogramming Christoforou, Nicolas; Chellappan, Malathi; Adler, Andrew F. PLoS ONE, Vol. 8, Issue 5 https://doi.org/10.1371/journal.pone.0063577	journal	May 2013
Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice Kothary, R.; Clapoff, S.; Darling, S. Development, Vol. 105, Issue 4 https://doi.org/10.1242/dev.105.4.707	journal	April 1989

Cited By (5)

Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling Wang, Zhaoning; Cui, Miao; Shah, Akansha M. Proceedings of the National Academy of Sciences, Vol. 116, Issue 37 https://doi.org/10.1073/pnas.1905824116	journal	August 2019
The genetic structure and adaptation of Andean highlanders and Amazonians are influenced by the interplay between geography and culture Borda, Víctor; Alvim, Isabela; Mendes, Marla Proceedings of the National Academy of Sciences, Vol. 117, Issue 51 https://doi.org/10.1073/pnas.2013773117	journal	December 2020
Landscape of Enhancer-Enhancer Cooperative Regulation during Human Cardiac Commitment Chen, Hong; Xiao, Jun; Shao, Tingting Molecular Therapy - Nucleic Acids, Vol. 17 https://doi.org/10.1016/j.omtn.2019.07.015	journal	September 2019
Ameliorating the Fibrotic Remodeling of the Heart through Direct Cardiac Reprogramming Bektik, Emre; Fu, Ji-dong Cells, Vol. 8, Issue 7 https://doi.org/10.3390/cells8070679	journal	July 2019
Intensive care for human hearts in pluripotent stem cell models Golforoush, Pelin; Schneider, Michael D. npj Regenerative Medicine, Vol. 5, Issue 1 https://doi.org/10.1038/s41536-020-0090-7	journal	March 2020

Similar Records

Smad4 mediated BMP2 signal is essential for the regulation of GATA4 and Nkx2.5 by affecting the histone H3 acetylation in H9c2 cells

Journal Article · Fri Jul 18 00:00:00 EDT 2014 · Biochemical and Biophysical Research Communications · OSTI ID:1650065

Si, Lina; Shi, Jin; Gao, Wenqun; +4 more

The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

Journal Article · Fri Oct 09 00:00:00 EDT 2009 · Biochemical and Biophysical Research Communications · OSTI ID:1650065

Munoz, Juan Pablo; Collao, Andres; Chiong, Mario; +9 more

HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development

Journal Article · Mon May 01 00:00:00 EDT 2017 · Cell Reports · OSTI ID:1650065

Laurent, Frédéric; Girdziusaite, Ausra; Gamart, Julie; +8 more

Related Subjects

60 APPLIED LIFE SCIENCES

Title: Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers

Citation Formats

References (78)

Cited By (5)

Similar Records

Related Subjects