NF-Y recruits Ash2L to impart H3K4 trimethylation on CCAAT promoters.

<h4>Background</h4>Different histone post-translational modifications (PTMs) are crucial in the regulation of chromatin, including methylations of H3 at Lysine 4 by the MLL complex. A relevant issue is how this is causally correlated to the binding of specific transcription factors (TFs)...

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Autores principales:	Andrea Fossati, Diletta Dolfini, Giacomo Donati, Roberto Mantovani
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a205be3448e4274ae29c1a9063dce66
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spelling	oai:doaj.org-article:4a205be3448e4274ae29c1a9063dce662021-11-18T06:57:05ZNF-Y recruits Ash2L to impart H3K4 trimethylation on CCAAT promoters.1932-620310.1371/journal.pone.0017220https://doaj.org/article/4a205be3448e4274ae29c1a9063dce662011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21445285/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Different histone post-translational modifications (PTMs) are crucial in the regulation of chromatin, including methylations of H3 at Lysine 4 by the MLL complex. A relevant issue is how this is causally correlated to the binding of specific transcription factors (TFs) in regulatory regions. NF-Y is a TF that regulates 30% of mammalian promoters containing the widespread CCAAT element. We and others established that the presence of H3K4me3 is dependent upon the binding of NF-Y. Here, we investigate the mechanisms of H3K4me3 deposition by NF-Y.<h4>Methods</h4>We employed Chromatin Immunoprecipitation in cells in which Ash2L and NF-Y subunits were knocked down by RNAi, to monitor the presence of histones PTMs and components of the MLL complex. We performed gene expression profiling of Ash2L-knocked down cells and analyzed the regulated genes. We performed ChIPs in leukemic cells in which MLL1 is devoid of the methyltransferase domain and fused to the AF4 gene.<h4>Results</h4>Knock down of the Ash2L subunit of MLL leads to a decrease in global H3K4me3 with a concomitant increase in H3K79me2. Knock down of NF-Y subunits prevents promoter association of Ash2L, but not MLL1, nor WDR5, and H3K4me3 drops dramatically. Endogenous NF-Y and Ash2L specifically interact in vivo. Analysis of the promoters of Ash2L regulated genes, identified by transcriptional profiling, suggests that a handful TF binding sites are moderately enriched, among which the CCAAT box. Finally, leukemic cells carrying the MLL-AF4 translocation show a decrease of H3K4me3, absence of Ash2L and increase in H3K79me2, while NF-Y binding was not significantly affected.<h4>Conclusions</h4>Three types of conclusions are reached: (i) H3K4 methylation is not absolutely required for NF-Y promoter association. (ii) NF-Y acts upstream of H3K4me3 deposition by recruiting Ash2L. (iii) There is a general cross-talk between H3K4me3 and H3K79me2 which is independent from the presence of MLL oncogenic fusions.Andrea FossatiDiletta DolfiniGiacomo DonatiRoberto MantovaniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17220 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrea Fossati Diletta Dolfini Giacomo Donati Roberto Mantovani NF-Y recruits Ash2L to impart H3K4 trimethylation on CCAAT promoters.
description	<h4>Background</h4>Different histone post-translational modifications (PTMs) are crucial in the regulation of chromatin, including methylations of H3 at Lysine 4 by the MLL complex. A relevant issue is how this is causally correlated to the binding of specific transcription factors (TFs) in regulatory regions. NF-Y is a TF that regulates 30% of mammalian promoters containing the widespread CCAAT element. We and others established that the presence of H3K4me3 is dependent upon the binding of NF-Y. Here, we investigate the mechanisms of H3K4me3 deposition by NF-Y.<h4>Methods</h4>We employed Chromatin Immunoprecipitation in cells in which Ash2L and NF-Y subunits were knocked down by RNAi, to monitor the presence of histones PTMs and components of the MLL complex. We performed gene expression profiling of Ash2L-knocked down cells and analyzed the regulated genes. We performed ChIPs in leukemic cells in which MLL1 is devoid of the methyltransferase domain and fused to the AF4 gene.<h4>Results</h4>Knock down of the Ash2L subunit of MLL leads to a decrease in global H3K4me3 with a concomitant increase in H3K79me2. Knock down of NF-Y subunits prevents promoter association of Ash2L, but not MLL1, nor WDR5, and H3K4me3 drops dramatically. Endogenous NF-Y and Ash2L specifically interact in vivo. Analysis of the promoters of Ash2L regulated genes, identified by transcriptional profiling, suggests that a handful TF binding sites are moderately enriched, among which the CCAAT box. Finally, leukemic cells carrying the MLL-AF4 translocation show a decrease of H3K4me3, absence of Ash2L and increase in H3K79me2, while NF-Y binding was not significantly affected.<h4>Conclusions</h4>Three types of conclusions are reached: (i) H3K4 methylation is not absolutely required for NF-Y promoter association. (ii) NF-Y acts upstream of H3K4me3 deposition by recruiting Ash2L. (iii) There is a general cross-talk between H3K4me3 and H3K79me2 which is independent from the presence of MLL oncogenic fusions.
format	article
author	Andrea Fossati Diletta Dolfini Giacomo Donati Roberto Mantovani
author_facet	Andrea Fossati Diletta Dolfini Giacomo Donati Roberto Mantovani
author_sort	Andrea Fossati
title	NF-Y recruits Ash2L to impart H3K4 trimethylation on CCAAT promoters.
title_short	NF-Y recruits Ash2L to impart H3K4 trimethylation on CCAAT promoters.
title_full	NF-Y recruits Ash2L to impart H3K4 trimethylation on CCAAT promoters.
title_fullStr	NF-Y recruits Ash2L to impart H3K4 trimethylation on CCAAT promoters.
title_full_unstemmed	NF-Y recruits Ash2L to impart H3K4 trimethylation on CCAAT promoters.
title_sort	nf-y recruits ash2l to impart h3k4 trimethylation on ccaat promoters.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/4a205be3448e4274ae29c1a9063dce66
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NF-Y recruits Ash2L to impart H3K4 trimethylation on CCAAT promoters.

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