title: A high definition look at the NF-Y regulome reveals genome-wide associations with selected transcription factors.
abstract: NF-Y is a trimeric transcription factor (TF), binding the CCAAT box element, for which several results suggest a pioneering role in activation of transcription. In this work, we integrated 380 ENCODE ChIP-Seq experiments for 154 TFs and cofactors with sequence analysis, protein-protein interactions and RNA profiling data, in order to identify genome-wide regulatory modules resulting from the co-association of NF-Y with other TFs. We identified three main degrees of co-association with NF-Y for sequence-specific TFs. In the most relevant one, we found TFs having a significant overlap with NF-Y in their DNA binding loci, some with a precise spacing of binding sites with respect to the CCAAT box, others (FOS, Sp1/2, RFX5, IRF3, PBX3) mostly lacking their canonical binding site and bound to arrays of well spaced CCAAT boxes. As expected, NF-Y binding also correlates with RNA Pol II General TFs and with subunits of complexes involved in the control of H3K4 methylations. Co-association patterns are confirmed by protein-protein interactions, and correspond to specific functional categorizations and expression level changes of target genes following NF-Y inactivation. These data define genome-wide rules for the organization of NF-Y-centered regulatory modules, supporting a model of distinct categorization and synergy with well defined sets of TFs.
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Via Celoria 26, 20133, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Dolfini
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Via Celoria 26, 20133, Italy Istituto di Biomembrane e Bioenergetica, Consiglio Nazionale delle Ricerche, Bari, Via Amendola 165/A, 70126, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Zambelli
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Via Celoria 26, 20133, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pedrazzoli
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Via Celoria 26, 20133, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mantovani
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Via Celoria 26, 20133, Italy giulio.pavesi@unimi.it.
authors.forename: Giulio
authors.initials: G
authors.lastname: Pavesi
mesh_terms: D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D023081:CCAAT-Binding Factor; D014157:Transcription Factors; D004247:DNA