Analysis of variation at transcription factor binding sites in Drosophila and humans
Name
gb-2012-13-9-r49.pdf
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2.49 MB
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Checksum (MD5)
1c2f45698aedf6c3fddf31404549e2c0
Author(s)
Spivakov, Mikhail
Akhtar, Junaid
Kheradpour, Pouya
Beal, Kathryn
Girardot, Charles
Koscielny, Gautier
Herrero, Javier
Kellis, Manolis
Furlong, Eileen E. M.
Birney, Ewan
Date Issued
September 2012
Journal
Genome Biology
Publisher
BioMed Central Ltd
Citation
Spivakov, Mikhail et al. “Analysis of Variation at Transcription Factor Binding Sites in Drosophila and Humans.” Genome Biology 13.9 (2012): R49. Web.
Version
Final published version
Abstract
Background: Advances in sequencing technology have boosted population genomics and made it possible to map the positions of transcription factor binding sites (TFBSs) with high precision. Here we investigate TFBS variability by combining transcription factor binding maps generated by ENCODE, modENCODE, our previously published data and other sources with genomic variation data for human individuals and Drosophila isogenic lines. Results: We introduce a metric of TFBS variability that takes into account changes in motif match associated with mutation and makes it possible to investigate TFBS functional constraints instance-by-instance as well as in sets that share common biological properties. We also take advantage of the emerging per-individual transcription factor binding data to show evidence that TFBS mutations, particularly at evolutionarily conserved sites, can be efficiently buffered to ensure coherent levels of transcription factor binding. Conclusions: Our analyses provide insights into the relationship between individual and interspecies variation and show evidence for the functional buffering of TFBS mutations in both humans and flies. In a broad perspective, these results demonstrate the potential of combining functional genomics and population genetics approaches for understanding gene regulation.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1186/gb-2012-13-9-r49
