NF-Y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.

The regulation of gene transcription requires posttranslational modifications of histones that, in concert with chromatin remodeling factors, shape the structure of chromatin. It is currently under intense investigation how this structure is modulated, in particular in the context of proliferation a...

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Autores principales:	Aymone Gurtner, Paola Fuschi, Fiorenza Magi, Claudia Colussi, Carlo Gaetano, Matthias Dobbelstein, Ada Sacchi, Giulia Piaggio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b95346c089f42608fca861079ce1854
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spelling	oai:doaj.org-article:7b95346c089f42608fca861079ce18542021-11-25T06:12:42ZNF-Y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.1932-620310.1371/journal.pone.0002047https://doaj.org/article/7b95346c089f42608fca861079ce18542008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18431504/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The regulation of gene transcription requires posttranslational modifications of histones that, in concert with chromatin remodeling factors, shape the structure of chromatin. It is currently under intense investigation how this structure is modulated, in particular in the context of proliferation and differentiation. Compelling evidence suggests that the transcription factor NF-Y acts as a master regulator of cell cycle progression, activating the transcription of many cell cycle regulatory genes. However, the underlying molecular mechanisms are not yet completely understood. Here we show that NF-Y exerts its effect on transcription through the modulation of the histone "code". NF-Y colocalizes with nascent RNA, while RNA polymerase II is I phosphorylated on serine 2 of the YSPTSPS repeats within its carboxyterminal domain and histones are carrying modifications that represent activation signals of gene expression (H3K9ac and PAN-H4ac). Comparing postmitotic muscle tissue from normal mice and proliferating muscles from mdx mice, we demonstrate by chromatin immunoprecipitation (ChIP) that NF-Y DNA binding activity correlates with the accumulation of acetylated histones H3 and H4 on promoters of key cell cycle regulatory genes, and with their active transcription. Accordingly, p300 is recruited onto the chromatin of NF-Y target genes in a NF-Y-dependent manner, as demonstrated by Re-ChIP. Conversely, the loss of NF-Y binding correlates with a decrease of acetylated histones, the recruitment of HDAC1, and a repressed heterochromatic state with enrichment of histones carrying modifications known to mediate silencing of gene expression (H3K9me3, H3K27me2 and H4K20me3). As a consequence, NF-Y target genes are downregulated in this context. In conclusion, our data indicate a role of NF-Y in modulating the structure and transcriptional competence of chromatin in vivo and support a model in which NF-Y-dependent histone "code" changes contribute to the proper discrimination between proliferating and postmitotic cells in vivo and in vitro.Aymone GurtnerPaola FuschiFiorenza MagiClaudia ColussiCarlo GaetanoMatthias DobbelsteinAda SacchiGiulia PiaggioPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 4, p e2047 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aymone Gurtner Paola Fuschi Fiorenza Magi Claudia Colussi Carlo Gaetano Matthias Dobbelstein Ada Sacchi Giulia Piaggio NF-Y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.
description	The regulation of gene transcription requires posttranslational modifications of histones that, in concert with chromatin remodeling factors, shape the structure of chromatin. It is currently under intense investigation how this structure is modulated, in particular in the context of proliferation and differentiation. Compelling evidence suggests that the transcription factor NF-Y acts as a master regulator of cell cycle progression, activating the transcription of many cell cycle regulatory genes. However, the underlying molecular mechanisms are not yet completely understood. Here we show that NF-Y exerts its effect on transcription through the modulation of the histone "code". NF-Y colocalizes with nascent RNA, while RNA polymerase II is I phosphorylated on serine 2 of the YSPTSPS repeats within its carboxyterminal domain and histones are carrying modifications that represent activation signals of gene expression (H3K9ac and PAN-H4ac). Comparing postmitotic muscle tissue from normal mice and proliferating muscles from mdx mice, we demonstrate by chromatin immunoprecipitation (ChIP) that NF-Y DNA binding activity correlates with the accumulation of acetylated histones H3 and H4 on promoters of key cell cycle regulatory genes, and with their active transcription. Accordingly, p300 is recruited onto the chromatin of NF-Y target genes in a NF-Y-dependent manner, as demonstrated by Re-ChIP. Conversely, the loss of NF-Y binding correlates with a decrease of acetylated histones, the recruitment of HDAC1, and a repressed heterochromatic state with enrichment of histones carrying modifications known to mediate silencing of gene expression (H3K9me3, H3K27me2 and H4K20me3). As a consequence, NF-Y target genes are downregulated in this context. In conclusion, our data indicate a role of NF-Y in modulating the structure and transcriptional competence of chromatin in vivo and support a model in which NF-Y-dependent histone "code" changes contribute to the proper discrimination between proliferating and postmitotic cells in vivo and in vitro.
format	article
author	Aymone Gurtner Paola Fuschi Fiorenza Magi Claudia Colussi Carlo Gaetano Matthias Dobbelstein Ada Sacchi Giulia Piaggio
author_facet	Aymone Gurtner Paola Fuschi Fiorenza Magi Claudia Colussi Carlo Gaetano Matthias Dobbelstein Ada Sacchi Giulia Piaggio
author_sort	Aymone Gurtner
title	NF-Y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.
title_short	NF-Y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.
title_full	NF-Y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.
title_fullStr	NF-Y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.
title_full_unstemmed	NF-Y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.
title_sort	nf-y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/7b95346c089f42608fca861079ce1854
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NF-Y dependent epigenetic modifications discriminate between proliferating and postmitotic tissue.

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