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Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions

Stewart MacArthur16, Xiao-Yong Li12, Jingyi Li3, James B Brown3, Hou Cheng Chu1, Lucy Zeng1, Brandi P Grondona1, Aaron Hechmer1, Lisa Simirenko1, Soile VE Keränen1, David W Knowles4, Mark Stapleton1, Peter Bickel3, Mark D Biggin1* and Michael B Eisen125*

Author affiliations

1 Genomics Division, Lawrence Berkeley National Laboratory, Cyclotron Road MS 84-181, Berkeley, CA 94720, USA

2 Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA

3 Department of Statistics, University of California Berkeley, Berkeley, CA 94720, USA

4 Life Sciences Division, Lawrence Berkeley National Laboratory, Cyclotron Road MS 84-181, Berkeley, CA 94720, USA

5 Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA

6 Current address: Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK

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Citation and License

Genome Biology 2009, 10:R80  doi:10.1186/gb-2009-10-7-r80

Published: 23 July 2009

Abstract

Background

We previously established that six sequence-specific transcription factors that initiate anterior/posterior patterning in Drosophila bind to overlapping sets of thousands of genomic regions in blastoderm embryos. While regions bound at high levels include known and probable functional targets, more poorly bound regions are preferentially associated with housekeeping genes and/or genes not transcribed in the blastoderm, and are frequently found in protein coding sequences or in less conserved non-coding DNA, suggesting that many are likely non-functional.

Results

Here we show that an additional 15 transcription factors that regulate other aspects of embryo patterning show a similar quantitative continuum of function and binding to thousands of genomic regions in vivo. Collectively, the 21 regulators show a surprisingly high overlap in the regions they bind given that they belong to 11 DNA binding domain families, specify distinct developmental fates, and can act via different cis-regulatory modules. We demonstrate, however, that quantitative differences in relative levels of binding to shared targets correlate with the known biological and transcriptional regulatory specificities of these factors.

Conclusions

It is likely that the overlap in binding of biochemically and functionally unrelated transcription factors arises from the high concentrations of these proteins in nuclei, which, coupled with their broad DNA binding specificities, directs them to regions of open chromatin. We suggest that most animal transcription factors will be found to show a similar broad overlapping pattern of binding in vivo, with specificity achieved by modulating the amount, rather than the identity, of bound factor.