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Proc Natl Acad Sci U S A DOI:10.1073/pnas.1804663115

Positional specificity of different transcription factor classes within enhancers.

Publication TypeJournal Article
Year of Publication2018
AuthorsGrossman, SR, Engreitz, J, Ray, JP, Nguyen, TH, Hacohen, N, Lander, ES
JournalProc Natl Acad Sci U S A
Date Published2018 Jul 24

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.


Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID29987030
PubMed Central IDPMC6065035
Grant ListT32 GM007753 / GM / NIGMS NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
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