Coregulation of transcription factor binding and nucleosome occupancy through DNA features of mammalian enhancers
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Transcription factors (TFs) preferentially bind sites contained in regions of computationally predicted high nucleosomal occupancy, suggesting that nucleosomes are gatekeepers of TF binding sites. However, because of their complexity mammalian genomes contain millions of randomly occurring, unbound TF consensus binding sites. We hypothesized that the information controlling nucleosome assembly may coincide with the information that enables TFs to bind cis-regulatory elements while ignoring randomly occurring sites. Hence, nucleosomes would selectively mask genomic sites that can be contacted by TFs and thus be potentially functional. The hematopoietic pioneer TF Pu.1 maintained nucleosome depletion at macrophage-specific enhancers that displayed a broad range of nucleosome occupancy in other cell types and in reconstituted chromatin. We identified a minimal set of DNA sequence and shape features that accurately predicted both Pu.1 binding and nucleosome occupancy genome-wide. These data reveal a basic organizational principle of mammalian cis-regulatory elements whereby TF recruitment and nucleosome deposition are controlled by overlapping DNA sequence features.
Date Issued
2014-06-05
Date Acceptance
2014-03-19
Citation
Molecular Cell, 2014, 54 (5), pp.844-857
ISSN
1097-2765
Publisher
Elsevier BV
Start Page
844
End Page
857
Journal / Book Title
Molecular Cell
Volume
54
Issue
5
Copyright Statement
© 2014 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
https://www.sciencedirect.com/science/article/pii/S1097276514003165?via%3Dihub
Subjects
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2014-05-08