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

Journal Article · · PLoS Biology (Online)
 [1];  [2];  [3];  [4];  [1];  [4];  [5];  [4];  [6]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Mathematics; Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
  2. Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division
  3. Univ. of Maryland, College Park, MD (United States). Center for Bioinformatics and Computational Biology
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division
  5. Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences; Univ. of California, Berkeley, CA (United States). Vincent J. Coates Genome Sequencing Lab.
  6. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences
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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 genomewide 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.

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:
1627162
Journal Information:
PLoS Biology (Online), Vol. 8, Issue 3; ISSN 1545-7885
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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