The histone-like NF-Y is a bifunctional transcription factor.
NF-Y is a trimeric transcription factor containing H2A/H2B-like subunits, which specifically binds to the CCAAT box, a common eukaryotic promoter element. To gain insights into NF-Y-dependent transcriptional regulation, we assessed its relationships with positive histone marks by chromatin immunoprecipitation-on-chip and correlative-profiling studies. Unbiased identification of binding sites shows that the majority of genes are bound by NF-Y in the promoter and/or within the coding region. Parallel analysis of H3K9-14ac and H3K4me3 sites indicates that NF-Y loci can be divided in two distinct clusters: (i) a large cohort contains H3K9-14ac and H3K4me3 marks and correlates with expression and (ii) a sizeable group is devoid of these marks and is found on transcriptionally silent genes. Within this class, we find that NF-Y binding is associated with negative histone marks, such as H4K20me3 and H3K27me3. NF-Y removal by a dominant negative NF-YA leads to a decrease in the transcription of expressed genes associated with H3K4me3 and H3K9-14ac, while increasing the levels of many inactive genes. These data indicate that NF-Y is embedded in positive as well as in negative methyl histone marks, serving a dual function in transcriptional regulation, as an activator or as a repressor.
Ceribelli
Michele
M
Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano, Via Celoria 26, 20133 Milano, Italy.
Dolfini
Diletta
D
Merico
Daniele
D
Gatta
Raffaella
R
Viganò
Alessandra M
AM
Pavesi
Giulio
G
Mantovani
Roberto
R
D000107:Acetylation; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D023081:CCAAT-Binding Factor; D006657:Histones; C492060:Nfya protein, mouse; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors