title: Integrative analysis of public ChIP-seq experiments reveals a complex multi-cell regulatory landscape.
abstract: The large collections of ChIP-seq data rapidly accumulating in public data warehouses provide genome-wide binding site maps for hundreds of transcription factors (TFs). However, the extent of the regulatory occupancy space in the human genome has not yet been fully apprehended by integrating public ChIP-seq data sets and combining it with ENCODE TFs map. To enable genome-wide identification of regulatory elements we have collected, analysed and retained 395 available ChIP-seq data sets merged with ENCODE peaks covering a total of 237 TFs. This enhanced repertoire complements and refines current genome-wide occupancy maps by increasing the human genome regulatory search space by 14% compared to ENCODE alone, and also increases the complexity of the regulatory dictionary. As a direct application we used this unified binding repertoire to annotate variant enhancer loci (VELs) from H3K4me1 mark in two cancer cell lines (MCF-7, CRC) and observed enrichments of specific TFs involved in biological key functions to cancer development and proliferation. Those enrichments of TFs within VELs provide a direct annotation of non-coding regions detected in cancer genomes. Finally, full access to this catalogue is available online together with the TFs enrichment analysis tool (http://tagc.univ-mrs.fr/remap/).
authors.affiliation: INSERM, UMR1090 TAGC, Marseille, F-13288, France Aix-Marseille Université, UMR1090 TAGC, Marseille, F-13288, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Griffon
authors.affiliation: INSERM, UMR1090 TAGC, Marseille, F-13288, France Aix-Marseille Université, UMR1090 TAGC, Marseille, F-13288, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Barbier
authors.affiliation: INSERM, UMR1090 TAGC, Marseille, F-13288, France Aix-Marseille Université, UMR1090 TAGC, Marseille, F-13288, France.
authors.forename: Jordi
authors.initials: J
authors.lastname: Dalino
authors.affiliation: INSERM, UMR1090 TAGC, Marseille, F-13288, France Aix-Marseille Université, UMR1090 TAGC, Marseille, F-13288, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: van Helden
authors.affiliation: INSERM, UMR1090 TAGC, Marseille, F-13288, France Aix-Marseille Université, UMR1090 TAGC, Marseille, F-13288, France.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Spicuglia
authors.affiliation: INSERM, UMR1090 TAGC, Marseille, F-13288, France Aix-Marseille Université, UMR1090 TAGC, Marseille, F-13288, France benoit.ballester@inserm.fr.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ballester
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D053263:Gene Regulatory Networks; D056426:Genetic Loci; D015894:Genome, Human; D006801:Humans; D020407:Internet; D061986:MCF-7 Cells; D058977:Molecular Sequence Annotation; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors