An NF-Y-dependent switch of positive and negative histone methyl marks on CCAAT promoters.
BACKGROUND
Histone tails have a plethora of different post-translational modifications, which are located differently in "open" and "closed" parts of genomes. H3K4me3/H3K79me2 and H4K20me3 are among the histone marks associated with the early establishment of active and inactive chromatin, respectively. One of the most widespread promoter elements is the CCAAT box, bound by the NF-Y trimer. Two of NF-Y subunits have an H2A-H2B-like structure.


RESULTS
We established the causal relationship between NF-Y binding and positioning of methyl marks, by ChIP analysis of mouse and human cells infected with a dominant negative NF-YA: a parallel decrease in NF-Y binding, H3K4me3, H3K79me2 and transcription was observed in promoters that are dependent upon NF-Y. On the contrary, changes in the levels of H3K9-14ac were more subtle. Components of the H3K4 methylating MLL complex are not recruited in the absence of NF-Y. As for repressed promoters, NF-Y removal leads to a decrease in the H4K20me3 mark and deposition of H3K4me3.


CONCLUSIONS
Two relevant findings are reported: (i) NF-Y gains access to its genomic locations independently from the presence of methyl histone marks, either positive or negative; (ii) NF-Y binding has profound positive or negative consequences on the deposition of histone methyl marks. Therefore NF-Y is a fundamental switch at the heart of decision between gene activation and repression in CCAAT regulated genes.
Donati
Giacomo
G
Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano, Milano, Italy.
Gatta
Raffaella
R
Dolfini
Diletta
D
Fossati
Andrea
A
Ceribelli
Michele
M
Mantovani
Roberto
R
D000818:Animals; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D045325:HCT116 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D023081:CCAAT-Binding Factor; D006657:Histones