Positional specificity of different transcription factor classes within enhancers
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Author(s) • • • • •
Engreitz, Jesse
Ray, John P.
Nguyen, Tung H.
Hacohen, Nir
Grossman, Sharon Rachel
Lander, Eric Steven
Date Issued
July 2018
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Grossman, Sharon R. et al. “Positional Specificity of Different Transcription Factor Classes Within Enhancers.” Proceedings of the National Academy of Sciences 115, 30 (July 2018): E7222–E7230 © 2018 National Academy of Sciences
Version
Final published version
Abstract
Gene expression is controlled by sequence-specific transcription factors (TFs), which bind to regulatory sequences in DNA. TF binding occurs in nucleosome-depleted regions of DNA (NDRs), which generally encompass regions with lengths similar to those protected by nucleosomes. However, less is known about where within these regions specific TFs tend to be found. Here, we characterize the positional bias of inferred binding sites for 103 TFs within ∼500,000 NDRs across 47 cell types. We find that distinct classes of TFs display different binding preferences: Some tend to have binding sites toward the edges, some toward the center, and some at other positions within the NDR. These patterns are highly consistent across cell types, suggesting that they may reflect TF-specific intrinsic structural or functional characteristics. In particular, TF classes with binding sites at NDR edges are enriched for those known to interact with histones and chromatin remodelers, whereas TFs with central enrichment interact with other TFs and cofactors such as p300. Our results suggest distinct regiospecific binding patterns and functions of TF classes within enhancers. Keywords: transcription factor binding; gene regulation; genomics; chromatin structure
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1804663115