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Nucleic Acids Res DOI:10.1093/nar/gkt1249

Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments.

Publication TypeJournal Article
Year of Publication2014
AuthorsKheradpour, P, Kellis, M
JournalNucleic Acids Res
Date Published2014 Mar
KeywordsBinding Sites, Cell Line, Chromatin Immunoprecipitation, Evolution, Molecular, Humans, Nucleotide Motifs, Regulatory Elements, Transcriptional, Sequence Analysis, DNA, Transcription Factors

Recent advances in technology have led to a dramatic increase in the number of available transcription factor ChIP-seq and ChIP-chip data sets. Understanding the motif content of these data sets is an important step in understanding the underlying mechanisms of regulation. Here we provide a systematic motif analysis for 427 human ChIP-seq data sets using motifs curated from the literature and also discovered de novo using five established motif discovery tools. We use a systematic pipeline for calculating motif enrichment in each data set, providing a principled way for choosing between motif variants found in the literature and for flagging potentially problematic data sets. Our analysis confirms the known specificity of 41 of the 56 analyzed factor groups and reveals motifs of potential cofactors. We also use cell type-specific binding to find factors active in specific conditions. The resource we provide is accessible both for browsing a small number of factors and for performing large-scale systematic analyses. We provide motif matrices, instances and enrichments in each of the ENCODE data sets. The motifs discovered here have been used in parallel studies to validate the specificity of antibodies, understand cooperativity between data sets and measure the variation of motif binding across individuals and species.


Alternate JournalNucleic Acids Res.
PubMed ID24335146
PubMed Central IDPMC3950668
Grant ListR01 HG004037 / HG / NHGRI NIH HHS / United States
HG004037 / HG / NHGRI NIH HHS / United States
HG006991 / HG / NHGRI NIH HHS / United States
HG007000 / HG / NHGRI NIH HHS / United States