J. Comput. Biol. - Integration of 198 ChIP-seq datasets reveals human cis-regulatory regions.

Tópicos

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Resumo

We analyzed 198 datasets of chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) and developed a methodology for identification of high-confidence enhancer and promoter regions from transcription factor ChIP-seq data alone. We identify 32,467 genomic regions marked with ChIP-seq binding peaks in 15 or more experiments as high-confidence cis-regulatory regions. Although the selected regions mark only ~0.67% of the genome, 70.5% of our predicted binding regions fall within independently identified, strongly expression-correlated and histone-marked enhancer regions, which cover ~8% of the genome (Ernst et al., Nature 2011 , 473, 43-49). Even more remarkably, 85.6% of our selected regions overlap transcription factor (TF) binding regions identified in evolutionarily conserved DNase1 hypersensitivity cluster regions, which cover 0.75% of the genome (Boyle et al., Genome Research 2011 , 21, 456-464). P-values for these overlaps are effectively zero (Z-scores of 328 and 715 respectively). Furthermore, 62% of our selected regions overlap the intersection of the evolutionarily conserved DNase1 hypersensitivity-identified TF-binding regions of Boyle et al. (2011) with the histone-marked enhancers found to be strongly associated with transcriptional activity by Ernst et al. (2011). Two hundred thirty of our candidate cis-regulatory regions overlap cancer-associated variants reported in the Catalogue of Somatic Mutations in Cancer ( http://www.sanger.ac.uk/genetics/CGP/cosmic/ ). We also identify 1,252 potential proximal promoters for the 7,561 disjoint lincRNA regions currently in the Human lincRNA Catalog (www.broadinstitute.org/genome_bio/human_lincrnas/). Our investigation used approximately half of all currently available ENCODE ChIP-seq datasets, suggesting further gains are likely from analysis of all datasets currently available.

Resumo Limpo

analyz dataset chromatin immunoprecipit follow high throughput sequenc chipseq develop methodolog identif highconfid enhanc promot region transcript factor chipseq data alon identifi genom region mark chipseq bind peak experi highconfid cisregulatori region although select region mark genom predict bind region fall within independ identifi strong expressioncorrel histonemark enhanc region cover genom ernst et al natur even remark select region overlap transcript factor tf bind region identifi evolutionarili conserv dnase hypersensit cluster region cover genom boyl et al genom research pvalu overlap effect zero zscore respect furthermor select region overlap intersect evolutionarili conserv dnase hypersensitivityidentifi tfbind region boyl et al histonemark enhanc found strong associ transcript activ ernst et al two hundr thirti candid cisregulatori region overlap cancerassoci variant report catalogu somat mutat cancer httpwwwsangeracukgeneticscgpcosm also identifi potenti proxim promot disjoint lincrna region current human lincrna catalog wwwbroadinstituteorggenomebiohumanlincrna investig use approxim half current avail encod chipseq dataset suggest gain like analysi dataset current avail

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