UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology

Date

9-2012

Document Type

Article

Medical Subject Headings

Base Composition; Binding Sites; Cell Line; *Chromatin Assembly and Disassembly; Chromatin Immunoprecipitation; Cluster Analysis; Computational Biology; Deoxyribonuclease I; *Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Internet; Molecular Sequence Annotation; Nucleosomes; Nucleotide Motifs; Organ Specificity; Protein Binding; Transcription Factors

Disciplines

Bioinformatics | Computational Biology | Genetics and Genomics | Molecular Genetics

Abstract

Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by the ENCODE Consortium. We identified highly enriched sequence motifs in most data sets, revealing new motifs and validating known ones. The motif sites (TF binding sites) are highly conserved evolutionarily and show distinct footprints upon DNase I digestion. We frequently detected secondary motifs in addition to the canonical motifs of the TFs, indicating tethered binding and cobinding between multiple TFs. We observed significant position and orientation preferences between many cobinding TFs. Genes specifically expressed in a cell line are often associated with a greater occurrence of nearby TF binding in that cell line. We observed cell-line-specific secondary motifs that mediate the binding of the histone deacetylase HDAC2 and the enhancer-binding protein EP300. TF binding sites are located in GC-rich, nucleosome-depleted, and DNase I sensitive regions, flanked by well-positioned nucleosomes, and many of these features show cell type specificity. The GC-richness may be beneficial for regulating TF binding because, when unoccupied by a TF, these regions are occupied by nucleosomes in vivo. We present the results of our analysis in a TF-centric web repository Factorbook (http://factorbook.org) and will continually update this repository as more ENCODE data are generated.

Rights and Permissions

Citation: Genome Res. 2012 Sep;22(9):1798-812. doi: 10.1101/gr.139105.112. Link to article on publisher's site

Comments

© 2012, Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.

Related Resources

Link to Article in PubMed

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