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Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors

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.

Reference

Wang J*, Zhuang J*, Iyer S*, Lin X*, Whitfield TW, Greven MC, Pierce BG, Dong X, Kundaje A, Cheng Y, Rando OJ, Birney E, Myers RM, Noble WS, Snyder M, Weng Z. (2012) Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. *Joint First Authors Genome Res. Sep;22(9):1798-812.

Jie Wang
Jiali Zhuang
Sowmya Iyer
Xin Lin
Troy W. Whitfield
Melissa C. Greven
Brian G. Pierce
Xianjun Dong
Anshul Kundaje
Yong Cheng
Oliver J. Rando
Ewan Birney
Richard M. Myers
William S. Noble
Michael Snyder
Zhiping Weng

Program in Bioinformatics and Integrative Biology
Department of Biochemistry and Molecular Pharmacology
University of Massachusetts Medical School
Worcester, MA 01605, USA

Ph: (508) 856-8866
Fx: (508) 856-2392
Zhiping.Weng@umassmed.edu