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Binding Site Turnover Produces Pervasive Quantitative Changes in Transcription Factor Binding between Closely Related Drosophila Species

Bradley, Robert K. and Li, Xiao-Yong and Trapnell, Cole and Davidson, Stuart and Pachter, Lior and Chu, Hou Cheng and Tonkin, Leath A. and Biggin, Mark D. and Eisen, Michael B. (2010) Binding Site Turnover Produces Pervasive Quantitative Changes in Transcription Factor Binding between Closely Related Drosophila Species. PLoS Biology, 8 (3). Art. No. e1000343. ISSN 1545-7885. PMCID PMC2843597. doi:10.1371/journal.pbio.1000343.

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Changes in gene expression play an important role in evolution, yet the molecular mechanisms underlying regulatory evolution are poorly understood. Here we compare genome-wide binding of the six transcription factors that initiate segmentation along the anterior-posterior axis in embryos of two closely related species: Drosophila melanogaster and Drosophila yakuba. Where we observe binding by a factor in one species, we almost always observe binding by that factor to the orthologous sequence in the other species. Levels of binding, however, vary considerably. The magnitude and direction of the interspecies differences in binding levels of all six factors are strongly correlated, suggesting a role for chromatin or other factor-independent forces in mediating the divergence of transcription factor binding. Nonetheless, factor-specific quantitative variation in binding is common, and we show that it is driven to a large extent by the gain and loss of cognate recognition sequences for the given factor. We find only a weak correlation between binding variation and regulatory function. These data provide the first genome-wide picture of how modest levels of sequence divergence between highly morphologically similar species affect a system of coordinately acting transcription factors during animal development, and highlight the dominant role of quantitative variation in transcription factor binding over short evolutionary distances.

Item Type:Article
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URLURL TypeDescription CentralArticle InTrends in computational biology—2010
Pachter, Lior0000-0002-9164-6231
Eisen, Michael B.0000-0002-7528-738X
Additional Information:This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Received: October 26, 2009; Accepted: February 17, 2010; Published: March 23, 2010. Experimental work described here was supported by a Howard Hughes Medical Institute Investigator award to MBE and by National Institutes of Health (NIH) grant GM704403 to MBE and MDB. Computational analyses were supported in by NIH grant HG002779 to MBE. Work at Lawrence Berkeley National Laboratory was conducted under Department of Energy contract DE-AC02-05CH11231. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Colin Dewey for providing a Mercator orthology mapping for D. melanogaster and D. yakuba and producing the alignment with FSA. We thank the members of the Eisen lab for many helpful discussions and comments on the manuscript. Author Contributions: The author(s) have made the following declarations about their contributions: Conceived and designed the experiments: RKB XYL MDB MBE. Performed the experiments: XYL HCC LAT. Analyzed the data: RKB CT SD LP MBE. Contributed reagents/materials/analysis tools: RKB CT LAT. Wrote the paper: RKB MBE. Competing interests: MBE is a co-founder and member of the Board of Directors of PLoS.
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Department of Energy (DOE)DE-AC02-05CH11231
Issue or Number:3
PubMed Central ID:PMC2843597
Record Number:CaltechAUTHORS:20170306-125457377
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Official Citation:Bradley RK, Li X-Y, Trapnell C, Davidson S, Pachter L, Chu HC, et al. (2010) Binding Site Turnover Produces Pervasive Quantitative Changes in Transcription Factor Binding between Closely Related Drosophila Species. PLoS Biol 8(3): e1000343. doi:10.1371/journal.pbio.1000343
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74792
Deposited By: George Porter
Deposited On:06 Mar 2017 21:46
Last Modified:11 Nov 2021 05:29

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