Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation

Hare, Emily E.; Peterson, Brant K.; Iyer, Venky N.; Meier, Rudolf; Eisen, Michael B.

doi:10.1371/journal.pgen.1000106

Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation

Journal Article · Fri Jun 27 00:00:00 EDT 2008 · PLoS Genetics

DOI:https://doi.org/10.1371/journal.pgen.1000106· OSTI ID:1627271

Hare, Emily E. ^[1]; Peterson, Brant K. ^[2]; Iyer, Venky N. ^[3]; Meier, Rudolf ^[4]; Eisen, Michael B. ^[5]

Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; DOE/OSTI
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Center for Integrative Genomics
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
National Univ. of Singapore (Singapore). Dept. of Biological Sciences
Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Center for Integrative Genomics; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; California Inst. for Quantitative Biosciences, Berkeley, CA (United States)

The gene expression pattern specified by an animal regulatory sequence is generally viewed as arising from the particular arrangement of transcription factor binding sites it contains. However, we demonstrate here that regulatory sequences whose binding sites have been almost completely rearranged can still produce identical outputs. We sequenced the evenskipped locus from six species of scavenger flies (Sepsidae) that are highly diverged from the model species Drosophila melanogaster, but share its basic patterns of developmental gene expression. Although there is little sequence similarity between the sepsid eve enhancers and their well-characterized D. melanogaster counterparts, the sepsid and Drosophila enhancers drive nearly identical expression patterns in transgenic D. melanogaster embryos. We conclude that the molecular machinery that connects regulatory sequences to the transcription apparatus is more flexible than previously appreciated. In exploring this diverse collection of sequences to identify the shared features that account for their similar functions, we found a small number of short (20–30 bp) sequences nearly perfectly conserved among the species. These highly conserved sequences are strongly enriched for pairs of overlapping or adjacent binding sites. Together, these observations suggest that the local arrangement of binding sites relative to each other is more important than their overall arrangement into larger units of cis-regulatory function.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1627271

Journal Information:: PLoS Genetics, Journal Name: PLoS Genetics Journal Issue: 6 Vol. 4; ISSN 1553-7404

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (64)

Characterization and localization of the even-skipped protein of Drosophila. Frasch, M.; Hoey, T.; Rushlow, C. The EMBO Journal, Vol. 6, Issue 3 https://doi.org/10.1002/j.1460-2075.1987.tb04817.x	journal	March 1987
The gap protein knirps mediates both quenching and direct repression in the Drosophila embryo. Arnosti, D. N.; Gray, S.; Barolo, S. The EMBO Journal, Vol. 15, Issue 14 https://doi.org/10.1002/j.1460-2075.1996.tb00735.x	journal	July 1996
Transcriptional Integration of Competence Modulated by Mutual Repression Generates Cell-Type Specificity within the Cardiogenic Mesoderm Han, Zhe; Fujioka, Miki; Su, Mingtsan Developmental Biology, Vol. 252, Issue 2 https://doi.org/10.1006/dbio.2002.0846	journal	December 2002
Turnover of binding sites for transcription factors involved in early Drosophila development Costas, Javier; Casares, Fernando; Vieira, Jorge Gene, Vol. 310 https://doi.org/10.1016/s0378-1119(03)00556-0	journal	May 2003
Specific expression of a silkencoding gene of Bombyx in the anterior salivary gland of Drosophila Bello, Bruno; Couble, Pierre Nature, Vol. 346, Issue 6283 https://doi.org/10.1038/346480a0	journal	August 1990
A self-organizing system of repressor gradients establishes segmental complexity in Drosophila Clyde, Dorothy E.; Corado, Maria S. G.; Wu, Xuelin Nature, Vol. 426, Issue 6968 https://doi.org/10.1038/nature02189	journal	December 2003
Creating transgenic Drosophila by microinjecting the site-specific φC31 integrase mRNA and a transgene-containing donor plasmid Fish, Matthew P.; Groth, Amy C.; Calos, Michele P. Nature Protocols, Vol. 2, Issue 10 https://doi.org/10.1038/nprot.2007.328	journal	September 2007
The evolutionary significance of cis-regulatory mutations Wray, Gregory A. Nature Reviews Genetics, Vol. 8, Issue 3 https://doi.org/10.1038/nrg2063	journal	March 2007
Genome-wide analysis of clustered Dorsal binding sites identifies putative target genes in the Drosophila embryo Markstein, M.; Markstein, P.; Markstein, V. Proceedings of the National Academy of Sciences, Vol. 99, Issue 2 https://doi.org/10.1073/pnas.012591199	journal	December 2001
Deciphering genetic regulatory codes: A challenge for functional genomics Michelson, Alan M. Proceedings of the National Academy of Sciences, Vol. 99, Issue 2 https://doi.org/10.1073/pnas.032685999	journal	January 2002
The anterior determinant bicoid of Drosophila is a derived Hox class 3 gene Stauber, M.; Jackle, H.; Schmidt-Ott, U. Proceedings of the National Academy of Sciences, Vol. 96, Issue 7 https://doi.org/10.1073/pnas.96.7.3786	journal	March 1999
PAML: a program package for phylogenetic analysis by maximum likelihood Yang, Ziheng Bioinformatics, Vol. 13, Issue 5 https://doi.org/10.1093/bioinformatics/13.5.555	journal	January 1997
Identifying DNA and protein patterns with statistically significant alignments of multiple sequences Hertz, G. Z.; Stormo, G. D. Bioinformatics, Vol. 15, Issue 7 https://doi.org/10.1093/bioinformatics/15.7.563	journal	July 1999
Drosophila DNase I footprint database: a systematic genome annotation of transcription factor binding sites in the fruitfly, Drosophila melanogaster Bergman, C. M.; Carlson, J. W.; Celniker, S. E. Bioinformatics, Vol. 21, Issue 8 https://doi.org/10.1093/bioinformatics/bti173	journal	November 2004
Evolution of Transcription Factor Binding Sites in Mammalian Gene Regulatory Regions: Conservation and Turnover Dermitzakis, Emmanouil T.; Clark, Andrew G. Molecular Biology and Evolution, Vol. 19, Issue 7 https://doi.org/10.1093/oxfordjournals.molbev.a004169	journal	July 2002
The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos. Jiang, J.; Kosman, D.; Ip, Y. T. Genes & Development, Vol. 5, Issue 10 https://doi.org/10.1101/gad.5.10.1881	journal	October 1991
Transcriptional regulation of a pair-rule stripe in Drosophila. Small, S.; Kraut, R.; Hoey, T. Genes & Development, Vol. 5, Issue 5 https://doi.org/10.1101/gad.5.5.827	journal	May 1991
Short-range repression permits multiple enhancers to function autonomously within a complex promoter. Gray, S.; Szymanski, P.; Levine, M. Genes & Development, Vol. 8, Issue 15 https://doi.org/10.1101/gad.8.15.1829	journal	August 1994
GeneWise and Genomewise Birney, E. Genome Research, Vol. 14, Issue 5 https://doi.org/10.1101/gr.1865504	journal	May 2004
Computation-Based Discovery of Related Transcriptional Regulatory Modules and Motifs Using an Experimentally Validated Combinatorial Model Halfon, Marc S.; Grad, Yonatan; Church, George M. Genome Research, Vol. 12, Issue 7 https://doi.org/10.1101/gr.228902	journal	July 2002
BLAT---The BLAST-Like Alignment Tool Kent, W. J. Genome Research, Vol. 12, Issue 4 https://doi.org/10.1101/gr.229202	journal	March 2002
Base-Calling of Automated Sequencer Traces Using Phred. I. Accuracy Assessment Ewing, Brent; Hillier, LaDeana; Wendl, Michael C. Genome Research, Vol. 8, Issue 3 https://doi.org/10.1101/gr.8.3.175	journal	March 1998
Base-Calling of Automated Sequencer Traces Using Phred. II. Error Probabilities Ewing, Brent; Green, Phil Genome Research, Vol. 8, Issue 3 https://doi.org/10.1101/gr.8.3.186	journal	March 1998
Human-Mouse Alignments with BLASTZ Schwartz, S. Genome Research, Vol. 13, Issue 1 https://doi.org/10.1101/gr.809403	journal	January 2003
LAGAN and Multi-LAGAN: Efficient Tools for Large-Scale Multiple Alignment of Genomic DNA Brudno, M. Genome Research, Vol. 13, Issue 4 https://doi.org/10.1101/gr.926603	journal	March 2003
Morphology versus molecules: the phylogenetic relationships of Sepsidae (Diptera: Cyclorrhapha) based on morphology and DNA sequence data from ten genes Feng-Yi Su, Kathy; Narayanan Kutty, Sujatha; Meier, Rudolf Cladistics, Vol. 24, Issue 6 https://doi.org/10.1111/j.1096-0031.2008.00222.x	journal	December 2008
Conservation of RET Regulatory Function from Human to Zebrafish Without Sequence Similarity Fisher, S. Science, Vol. 312, Issue 5771 https://doi.org/10.1126/science.1124070	journal	April 2006
Phylogenetic Simulation of Promoter Evolution: Estimation and Modeling of Binding Site Turnover Events and Assessing Their Impact on Alignment Tools Huang, Weichun; Nevins, Joseph R.; Ohler, Uwe Genome Biology, Vol. 8, Issue 10 https://doi.org/10.1186/gb-2007-8-10-r225	journal	January 2007
Information display by transcriptional enhancers Kulkarni, M. M. Development, Vol. 130, Issue 26 https://doi.org/10.1242/dev.00890	journal	December 2003
A regulatory code for neurogenic gene expression in the Drosophila embryo Markstein, M. Development, Vol. 131, Issue 10 https://doi.org/10.1242/dev.01124	journal	April 2004
The eve stripe 2 enhancer employs multiple modes of transcriptional synergy Arnosti, D. N.; Barolo, S.; Levine, M. Development, Vol. 122, Issue 1 https://doi.org/10.1242/dev.122.1.205	journal	January 1996
Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change Ludwig, M. Z.; Patel, N. H.; Kreitman, M. Development, Vol. 125, Issue 5 https://doi.org/10.1242/dev.125.5.949	journal	March 1998
Analysis of an even-skipped rescue transgene reveals both composite and discrete neuronal and early blastoderm enhancers, and multi-stripe positioning by gap gene repressor gradients Fujioka, M.; Emi-Sarker, Y.; Yusibova, G. L. Development, Vol. 126, Issue 11 https://doi.org/10.1242/dev.126.11.2527	journal	June 1999
Regulation of even-skipped stripe 2 in the Drosophila embryo. Small, S.; Blair, A.; Levine, M. The EMBO Journal, Vol. 11, Issue 11 https://doi.org/10.1002/j.1460-2075.1992.tb05498.x	journal	November 1992
Regulation of Two Pair-Rule Stripes by a Single Enhancer in theDrosophilaEmbryo Small, Stephen; Blair, Adrienne; Levine, Michael Developmental Biology, Vol. 175, Issue 2 https://doi.org/10.1006/dbio.1996.0117	journal	May 1996
Control of Cardiac Development by an Evolutionarily Conserved Transcriptional Network Cripps, Richard M.; Olson, Eric N. Developmental Biology, Vol. 246, Issue 1 https://doi.org/10.1006/dbio.2002.0666	journal	June 2002
T-coffee: a novel method for fast and accurate multiple sequence alignment 1 1Edited by J. Thornton Notredame, Cédric; Higgins, Desmond G.; Heringa, Jaap Journal of Molecular Biology, Vol. 302, Issue 1 https://doi.org/10.1006/jmbi.2000.4042	journal	September 2000
Identification of a Stat Gene That Functions in Drosophila Development Yan, Riqiang; Small, Stephen; Desplan, Claude Cell, Vol. 84, Issue 3 https://doi.org/10.1016/S0092-8674(00)81287-8	journal	February 1996
Turnover of binding sites for transcription factors involved in early Drosophila development Costas, Javier; Casares, Fernando; Vieira, Jorge Gene, Vol. 310 https://doi.org/10.1016/S0378-1119(03)00556-0	journal	May 2003
An Atomic Model of the Interferon-β Enhanceosome Panne, Daniel; Maniatis, Tom; Harrison, Stephen C. Cell, Vol. 129, Issue 6 https://doi.org/10.1016/j.cell.2007.05.019	journal	June 2007
Different combinations of gap repressors for common stripes in Anopheles and Drosophila embryos Goltsev, Yury; Hsiong, William; Lanzaro, Gregory Developmental Biology, Vol. 275, Issue 2 https://doi.org/10.1016/j.ydbio.2004.08.021	journal	November 2004
DNA loss and evolution of genome size in Drosophila Petrov, Dmitri A. Genetica, Vol. 115, Issue 1, p. 81-91 https://doi.org/10.1023/A:1016076215168	journal	January 2002
Regulatory elements controlling chorion gene expression are conserved between flies and moths Mitsialis, S. Alex; Kafatos, Fotis C. Nature, Vol. 317, Issue 6036 https://doi.org/10.1038/317453a0	journal	October 1985
Evidence for stabilizing selection in a eukaryotic enhancer element Ludwig, Michael Z.; Bergman, Casey; Patel, Nipam H. Nature, Vol. 403, Issue 6769 https://doi.org/10.1038/35000615	journal	February 2000
Quantitative and predictive model of transcriptional control of the Drosophila melanogaster even skipped gene Janssens, Hilde; Hou, Shuling; Jaeger, Johannes Nature Genetics, Vol. 38, Issue 10 https://doi.org/10.1038/ng1886	journal	September 2006
Exploiting transcription factor binding site clustering to identify cis-regulatory modules involved in pattern formation in the Drosophila genome Berman, B. P.; Nibu, Y.; Pfeiffer, B. D. Proceedings of the National Academy of Sciences, Vol. 99, Issue 2 https://doi.org/10.1073/pnas.231608898	journal	January 2002
Comparisons with Caenorhabditis (100 Mb) and Drosophila (175 Mb) Using Flow Cytometry Show Genome Size in Arabidopsis to be 157 Mb and thus 25 % Larger than the Arabidopsis Genome Initiative Estimate of 125 Mb Bennett, M. D. Annals of Botany, Vol. 91, Issue 5 https://doi.org/10.1093/aob/mcg057	journal	February 2003
REDfly: a Regulatory Element Database for Drosophila Gallo, S. M.; Li, L.; Hu, Z. Bioinformatics, Vol. 22, Issue 3 https://doi.org/10.1093/bioinformatics/bti794	journal	November 2005
Improved likelihood ratio tests for complete contingency tables Williams, D. A. Biometrika, Vol. 63, Issue 1 https://doi.org/10.1093/biomet/63.1.33	journal	January 1976
Tracing the Evolutionary History of Drosophila Regulatory Regions with Models that Identify Transcription Factor Binding Sites Dermitzakis, E. T. Molecular Biology and Evolution, Vol. 20, Issue 5 https://doi.org/10.1093/molbev/msg077	journal	April 2003
Short-range transcriptional repressors mediate both quenching and direct repression within complex loci in Drosophila. Gray, S.; Levine, M. Genes & Development, Vol. 10, Issue 6 https://doi.org/10.1101/gad.10.6.700	journal	March 1996
Analysis of Conserved Noncoding DNA in Drosophila Reveals Similar Constraints in Intergenic and Intronic Sequences Bergman, C. M. Genome Research, Vol. 11, Issue 8 https://doi.org/10.1101/gr.178701	journal	August 2001
ARACHNE: A Whole-Genome Shotgun Assembler Batzoglou, S. Genome Research, Vol. 12, Issue 1 https://doi.org/10.1101/gr.208902	journal	January 2002
Whole-Genome Sequence Assembly for Mammalian Genomes: Arachne 2 Jaffe, D. B. Genome Research, Vol. 13, Issue 1 https://doi.org/10.1101/gr.828403	journal	January 2003
Evolutionary and functional analysis of the tailless enhancer in Musca domestica and Drosophila melanogaster Wratten, Naomi S.; McGregor, Alistair P.; Shaw, Philip J. Evolution Development, Vol. 8, Issue 1 https://doi.org/10.1111/j.1525-142X.2006.05070.x	journal	January 2006
The Genome Sequence of the Malaria Mosquito Anopheles gambiae Holt, Robert A.; Subramanian, G. Mani; Halpern, Aaron Science, Vol. 298, Issue 5591 https://doi.org/10.1126/science.1076181	journal	October 2002
Regulation of a segmentation stripe by overlapping activators and repressors in the Drosophila embryo Stanojevic, D.; Small, S.; Levine, M. Science, Vol. 254, Issue 5036 https://doi.org/10.1126/science.1683715	journal	November 1991
A NALYSIS AND F UNCTION OF T RANSCRIPTIONAL R EGULATORY E LEMENTS : Insights from Drosophila Arnosti, David N. Annual Review of Entomology, Vol. 48, Issue 1 https://doi.org/10.1146/annurev.ento.48.091801.112749	journal	January 2003
Phylogeny and systematics of Diptera: Two decades of progress and prospects* Yeates, David K.; Wiegmann, Brian M.; Courtney, Greg W. Zootaxa, Vol. 1668, Issue 1 https://doi.org/10.11646/zootaxa.1668.1.27	journal	December 2007
Cross-species comparison significantly improves genome-wide prediction of cis-regulatory modules in Drosophila Sinha, Saurabh; Schroeder, Mark D.; Unnerstall, Ulrich BMC Bioinformatics, Vol. 5, Issue 1, p. 129 https://doi.org/10.1186/1471-2105-5-129	journal	January 2004
Computational identification of developmental enhancers: conservation and function of transcription factor binding-site clusters in Drosophila melanogaster and Drosophila pseudoobscura Berman, Benjamin P.; Pfeiffer, Barret D.; Laverty, Todd R. Genome Biology, Vol. 5, Issue 9, p. R61 https://doi.org/10.1186/gb-2004-5-9-r61	journal	January 2004
Functional Evolution of a cis-Regulatory Module Ludwig, Michael Z.; Palsson, Arnar; Alekseeva, Elena PLoS Biology, Vol. 3, Issue 4 https://doi.org/10.1371/journal.pbio.0030093	journal	March 2005
Large-Scale Turnover of Functional Transcription Factor Binding Sites in Drosophila Moses, Alan M.; Pollard, Daniel A.; Nix, David A. PLoS Computational Biology, Vol. 2, Issue 10 https://doi.org/10.1371/journal.pcbi.0020130	journal	January 2006
Construction of Transgenic Drosophila by Using the Site-Specific Integrase From Phage C31 Groth, A. C. Genetics, Vol. 166, Issue 4 https://doi.org/10.1534/genetics.166.4.1775	journal	April 2004

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The gap gene network Jaeger, Johannes Cellular and Molecular Life Sciences, Vol. 68, Issue 2 https://doi.org/10.1007/s00018-010-0536-y	journal	October 2010
Cis-regulatory architecture of a brain signaling center predates the origin of chordates Yao, Yao; Minor, Paul J.; Zhao, Ying-Tao Nature Genetics, Vol. 48, Issue 5 https://doi.org/10.1038/ng.3542	journal	April 2016
Epigenomic annotation of gene regulatory alterations during evolution of the primate brain Vermunt, Marit W.; Tan, Sander C.; Castelijns, Bas Nature Neuroscience, Vol. 19, Issue 3 https://doi.org/10.1038/nn.4229	journal	January 2016
Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence Wittkopp, Patricia J.; Kalay, Gizem Nature Reviews Genetics, Vol. 13, Issue 1 https://doi.org/10.1038/nrg3095	journal	December 2011
Evolution of transcription factor binding in metazoans — mechanisms and functional implications Villar, Diego; Flicek, Paul; Odom, Duncan T. Nature Reviews Genetics, Vol. 15, Issue 4 https://doi.org/10.1038/nrg3481	journal	March 2014
The appeasement of Doug: a synthetic approach to enhancer biology Vincent, Ben J.; Estrada, Javier; DePace, Angela H. Integrative Biology, Vol. 8, Issue 4 https://doi.org/10.1039/c5ib00321k	journal	March 2016
Conserved regulatory architecture underlies parallel genetic changes and convergent phenotypic evolution Frankel, N.; Wang, S.; Stern, D. L. Proceedings of the National Academy of Sciences, Vol. 109, Issue 51 https://doi.org/10.1073/pnas.1207715109	journal	November 2012
Evolutionary meandering of intermolecular interactions along the drift barrier Lynch, Michael; Hagner, Kyle Proceedings of the National Academy of Sciences, Vol. 112, Issue 1 https://doi.org/10.1073/pnas.1421641112	journal	December 2014
ChIP-ping the branches of the tree: functional genomics and the evolution of eukaryotic gene regulation Marinov, Georgi K.; Kundaje, Anshul Briefings in Functional Genomics, Vol. 17, Issue 2 https://doi.org/10.1093/bfgp/ely004	journal	February 2018
Phylogenetic Modeling of Regulatory Element Turnover Based on Epigenomic Data Dukler, Noah; Huang, Yi-Fei; Siepel, Adam Molecular Biology and Evolution, Vol. 37, Issue 7 https://doi.org/10.1093/molbev/msaa073	journal	March 2020
Structural properties of genotype–phenotype maps Ahnert, S. E. Journal of The Royal Society Interface, Vol. 14, Issue 132 https://doi.org/10.1098/rsif.2017.0275	journal	July 2017
Evolution of transcriptional enhancers and animal diversity Rubinstein, Marcelo; de Souza, Flávio S. J. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 368, Issue 1632 https://doi.org/10.1098/rstb.2013.0017	journal	December 2013
The structure and evolution of cis -regulatory regions: the shavenbaby story Stern, David L.; Frankel, Nicolás Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 368, Issue 1632 https://doi.org/10.1098/rstb.2013.0028	journal	December 2013
Waiting in the wings: what can we learn about gene co-option from the diversification of butterfly wing patterns? Jiggins, Chris D.; Wallbank, Richard W. R.; Hanly, Joseph J. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 372, Issue 1713 https://doi.org/10.1098/rstb.2015.0485	journal	February 2017
Cis-regulatory evolution integrated the Bric-à-brac transcription factors into a novel fruit fly gene regulatory network Roeske, Maxwell J.; Camino, Eric M.; Grover, Sumant https://doi.org/10.1101/200360	posted_content	October 2017
System drift and speciation Schiffman, Joshua S.; Ralph, Peter L. Evolution https://doi.org/10.1101/231209	posted_content	January 2018
The role of chromatin accessibility in cis-regulatory evolution Peng, Pei-Chen; Khoueiry, Pierre; Girardot, Charles Genome Biology and Evolution https://doi.org/10.1101/319046	journal	October 2018
Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity Park, Jeehae; Estrada, Javier; Johnson, Gemma eLife https://doi.org/10.1101/408708	journal	January 2018
Redundant and cryptic enhancer activities of the Drosophila yellow gene Kalay, Gizem; Lachowiec, Jennifer; Rosas, Ulises Genetics https://doi.org/10.1101/419226	posted_content	September 2018
Early origin and deep conservation of enhancers in animals Wong, Emily S.; Tan, Siew Zhuan; Garside, Victoria https://doi.org/10.1101/633651	posted_content	January 2019
Phylogenetic modeling of regulatory element turnover based on epigenomic data Dukler, Noah; Huang, Yi-Fei; Siepel, Adam Molecular Biology and Evolution https://doi.org/10.1101/773614	journal	September 2019
Cooperative recruitment of Yan via a high-affinity ETS supersite organizes repression to confer specificity and robustness to cardiac cell fate specification Boisclair Lachance, Jean-François; Webber, Jemma L.; Hong, Lu Genes & Development, Vol. 32, Issue 5-6 https://doi.org/10.1101/gad.307132.117	journal	March 2018
Molecular dissection of the genetic mechanisms that underlie expression conservation in orthologous yeast ribosomal promoters Zeevi, Danny; Lubliner, Shai; Lotan-Pompan, Maya Genome Research, Vol. 24, Issue 12 https://doi.org/10.1101/gr.179259.114	journal	October 2014
System drift and speciation Schiffman, Joshua S.; Ralph, Peter L. Evolution https://doi.org/10.1111/evo.14356	journal	October 2021
In silico evolution of the Drosophila gap gene regulatory sequence under elevated mutational pressure Chertkova, Aleksandra A.; Schiffman, Joshua S.; Nuzhdin, Sergey V. BMC Evolutionary Biology, Vol. 17, Issue S1 https://doi.org/10.1186/s12862-016-0866-y	journal	February 2017
Synthetic enhancer design by in silico compensatory evolution reveals flexibility and constraint in cis-regulation Barr, Kenneth A.; Martinez, Carlos; Moran, Jennifer R. BMC Systems Biology, Vol. 11, Issue 1 https://doi.org/10.1186/s12918-017-0485-2	journal	November 2017
McEnhancer: predicting gene expression via semi-supervised assignment of enhancers to target genes Hafez, Dina; Karabacak, Aslihan; Krueger, Sabrina Genome Biology, Vol. 18, Issue 1 https://doi.org/10.1186/s13059-017-1316-x	journal	October 2017
Arthropod segmentation Clark, Erik; Peel, Andrew D.; Akam, Michael Development, Vol. 146, Issue 18 https://doi.org/10.1242/dev.170480	journal	September 2019
Evolution of Regulatory Sequences in 12 Drosophila Species Kim, Jaebum; He, Xin; Sinha, Saurabh PLoS Genetics, Vol. 5, Issue 1 https://doi.org/10.1371/journal.pgen.1000330	journal	January 2009
A Machine Learning Approach for Identifying Novel Cell Type–Specific Transcriptional Regulators of Myogenesis Busser, Brian W.; Taher, Leila; Kim, Yongsok PLoS Genetics, Vol. 8, Issue 3 https://doi.org/10.1371/journal.pgen.1002531	journal	March 2012
Hunchback is counter-repressed to regulate even-skipped stripe 2 expression in Drosophila embryos Vincent, Ben J.; Staller, Max V.; Lopez-Rivera, Francheska PLOS Genetics, Vol. 14, Issue 9 https://doi.org/10.1371/journal.pgen.1007644	journal	September 2018
Redundant and Cryptic Enhancer Activities of the Drosophila yellow Gene Kalay, Gizem; Lachowiec, Jennifer; Rosas, Ulises Genetics, Vol. 212, Issue 1 https://doi.org/10.1534/genetics.119.301985	journal	March 2019
Structural properties of genotype-phenotype maps. Ahnert, Sebastian Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.10711	text	January 2017
Arthropod segmentation. Clark, Erik; Peel, Andrew D.; Akam, Michael The Company of Biologists https://doi.org/10.17863/cam.43111	journalarticle	January 2019
Waiting in the wings: what can we learn about gene co-option from the diversification of butterfly wing patterns? Jiggins, Chris; Wallbank, Richard; Hanly, Joseph Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.6980	text	January 2017
Ultraconserved non-coding DNA within insect phyla Brody, Thomas; Yavatkar, Amar; Kuzin, Alexander https://doi.org/10.21203/rs.2.14345/v1	posted_content	September 2019
Genome-wide errant targeting by Hairy Kok, Kurtulus; Ay, Ahmet; Li, Li M. eLife, Vol. 4 https://doi.org/10.7554/eLife.06394	journal	August 2015
Divergent mechanisms regulate conserved cardiopharyngeal development and gene expression in distantly related ascidians Stolfi, Alberto; Lowe, Elijah K.; Racioppi, Claudia eLife, Vol. 3 https://doi.org/10.7554/elife.03728	journal	September 2014
Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity Park, Jeehae; Estrada, Javier; Johnson, Gemma eLife, Vol. 8 https://doi.org/10.7554/elife.41266	journal	June 2019

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