RT Journal
A1 Wang, Jie
A1 Zhuang, Jiali
A1 Iyer, Sowmya
A1 Lin, XinYing
A1 Whitfield, Troy W.
A1 Greven, Melissa C.
A1 Pierce, Brian G.
A1 Dong, Xianjun
A1 Kundaje, Anshul
A1 Cheng, Yong
A1 Rando, Oliver J.
A1 Birney, Ewan
A1 Myers, Richard M.
A1 Noble, William S.
A1 Snyder, Michael
A1 Weng, Zhiping
T1 Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors
JF Genome Research 
JO Genome Research 
YR 2012 
FD September 01 
VO 22 
IS 9 
SP 1798 
OP 1812 
DO 10.1101/gr.139105.112 
UL http://genome.cshlp.org/content/22/9/1798.abstract 
AB 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.