Analysis of Myc-induced histone modifications on target chromatin.

The c-myc proto-oncogene is induced by mitogens and is a central regulator of cell growth and differentiation. The c-myc product, Myc, is a transcription factor that binds a multitude of genomic sites, estimated to be over 10-15% of all promoter regions. Target promoters generally pre-exist in an ac...

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Main Authors: Francesca Martinato, Matteo Cesaroni, Bruno Amati, Ernesto Guccione
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2574517?pdf=render
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spelling doaj-1ce929c1bc004062b6d2a8a3c02061c22020-11-25T02:29:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01311e365010.1371/journal.pone.0003650Analysis of Myc-induced histone modifications on target chromatin.Francesca MartinatoMatteo CesaroniBruno AmatiErnesto GuccioneThe c-myc proto-oncogene is induced by mitogens and is a central regulator of cell growth and differentiation. The c-myc product, Myc, is a transcription factor that binds a multitude of genomic sites, estimated to be over 10-15% of all promoter regions. Target promoters generally pre-exist in an active or poised chromatin state that is further modified by Myc, contributing to fine transcriptional regulation (activation or repression) of the afferent gene. Among other mechanisms, Myc recruits histone acetyl-transferases to target chromatin and locally promotes hyper-acetylation of multiple lysines on histones H3 and H4, although the identity and combination of the modified lysines is unknown. Whether Myc dynamically regulates other histone modifications (or marks) at its binding sites also remains to be addressed. Here, we used quantitative chromatin immunoprecipitation (qChIP) to profile a total of 24 lysine-acetylation and -methylation marks modulated by Myc at target promoters in a human B-cell line with a regulatable c-myc transgene. Myc binding promoted acetylation of multiple lysines, primarily of H3K9, H3K14, H3K18, H4K5 and H4K12, but significantly also of H4K8, H4K91 and H2AK5. Dimethylation of H3K79 was also selectively induced at target promoters. A majority of target promoters showed co-induction of multiple marks - in various combinations - correlating with recruitment of the two HATs tested (Tip60 and HBO1), incorporation of the histone variant H2A.Z and transcriptional activation. Based on this and previous findings, we surmise that Myc recruits the Tip60/p400 complex to achieve a coordinated histone acetylation/exchange reaction at activated promoters. Our data are also consistent with the additive and redundant role of multiple acetylation events in transcriptional activation.http://europepmc.org/articles/PMC2574517?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Francesca Martinato
Matteo Cesaroni
Bruno Amati
Ernesto Guccione
spellingShingle Francesca Martinato
Matteo Cesaroni
Bruno Amati
Ernesto Guccione
Analysis of Myc-induced histone modifications on target chromatin.
PLoS ONE
author_facet Francesca Martinato
Matteo Cesaroni
Bruno Amati
Ernesto Guccione
author_sort Francesca Martinato
title Analysis of Myc-induced histone modifications on target chromatin.
title_short Analysis of Myc-induced histone modifications on target chromatin.
title_full Analysis of Myc-induced histone modifications on target chromatin.
title_fullStr Analysis of Myc-induced histone modifications on target chromatin.
title_full_unstemmed Analysis of Myc-induced histone modifications on target chromatin.
title_sort analysis of myc-induced histone modifications on target chromatin.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2008-01-01
description The c-myc proto-oncogene is induced by mitogens and is a central regulator of cell growth and differentiation. The c-myc product, Myc, is a transcription factor that binds a multitude of genomic sites, estimated to be over 10-15% of all promoter regions. Target promoters generally pre-exist in an active or poised chromatin state that is further modified by Myc, contributing to fine transcriptional regulation (activation or repression) of the afferent gene. Among other mechanisms, Myc recruits histone acetyl-transferases to target chromatin and locally promotes hyper-acetylation of multiple lysines on histones H3 and H4, although the identity and combination of the modified lysines is unknown. Whether Myc dynamically regulates other histone modifications (or marks) at its binding sites also remains to be addressed. Here, we used quantitative chromatin immunoprecipitation (qChIP) to profile a total of 24 lysine-acetylation and -methylation marks modulated by Myc at target promoters in a human B-cell line with a regulatable c-myc transgene. Myc binding promoted acetylation of multiple lysines, primarily of H3K9, H3K14, H3K18, H4K5 and H4K12, but significantly also of H4K8, H4K91 and H2AK5. Dimethylation of H3K79 was also selectively induced at target promoters. A majority of target promoters showed co-induction of multiple marks - in various combinations - correlating with recruitment of the two HATs tested (Tip60 and HBO1), incorporation of the histone variant H2A.Z and transcriptional activation. Based on this and previous findings, we surmise that Myc recruits the Tip60/p400 complex to achieve a coordinated histone acetylation/exchange reaction at activated promoters. Our data are also consistent with the additive and redundant role of multiple acetylation events in transcriptional activation.
url http://europepmc.org/articles/PMC2574517?pdf=render
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