title: NF-Y coassociates with FOS at promoters, enhancers, repetitive elements, and inactive chromatin regions, and is stereo-positioned with growth-controlling transcription factors.
abstract: NF-Y, a trimeric transcription factor (TF) composed of two histone-like subunits (NF-YB and NF-YC) and a sequence-specific subunit (NF-YA), binds to the CCAAT motif, a common promoter element. Genome-wide mapping reveals 5000-15,000 NF-Y binding sites depending on the cell type, with the NF-YA and NF-YB subunits binding asymmetrically with respect to the CCAAT motif. Despite being characterized as a proximal promoter TF, only 25% of NF-Y sites map to promoters. A comparable number of NF-Y sites are located at enhancers, many of which are tissue specific, and nearly half of the NF-Y sites are in select subclasses of HERV LTR repeats. Unlike most TFs, NF-Y can access its target DNA motif in inactive (nonmodified) or polycomb-repressed chromatin domains. Unexpectedly, NF-Y extensively colocalizes with FOS in all genomic contexts, and this often occurs in the absence of JUN and the AP-1 motif. NF-Y also coassociates with a select cluster of growth-controlling and oncogenic TFs, consistent with the abundance of CCAAT motifs in the promoters of genes overexpressed in cancer. Interestingly, NF-Y and several growth-controlling TFs bind in a stereo-specific manner, suggesting a mechanism for cooperative action at promoters and enhancers. Our results indicate that NF-Y is not merely a commonly used proximal promoter TF, but rather performs a more diverse set of biological functions, many of which are likely to involve coassociation with FOS.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Fleming
authors.forename: Giulio
authors.initials: G
authors.lastname: Pavesi
authors.forename: Paolo
authors.initials: P
authors.lastname: Benatti
authors.forename: Carol
authors.initials: C
authors.lastname: Imbriano
authors.forename: Roberto
authors.initials: R
authors.lastname: Mantovani
authors.forename: Kevin
authors.initials: K
authors.lastname: Struhl
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D016384:Consensus Sequence; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D063990:Gene Ontology; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D058977:Molecular Sequence Annotation; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D020079:Terminal Repeat Sequences; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D023081:CCAAT-Binding Factor; D002843:Chromatin; C492061:NFYA protein, human; C492063:NFYB protein, human; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors