The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.

Patterns of methylation at lysine 4 and 27 of histone H3 have been associated with states of gene activation and repression that are developmentally regulated and are thought to underlie the establishment of lineage specific gene expression programs. Recent studies have provided fundamental insight...

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Autores principales:	Thomas Burgold, Fabio Spreafico, Francesca De Santa, Maria Grazia Totaro, Elena Prosperini, Gioacchino Natoli, Giuseppe Testa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8431b88aec124da98c71019e648380d5
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spelling	oai:doaj.org-article:8431b88aec124da98c71019e648380d52021-11-25T06:18:54ZThe histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.1932-620310.1371/journal.pone.0003034https://doaj.org/article/8431b88aec124da98c71019e648380d52008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18716661/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Patterns of methylation at lysine 4 and 27 of histone H3 have been associated with states of gene activation and repression that are developmentally regulated and are thought to underlie the establishment of lineage specific gene expression programs. Recent studies have provided fundamental insight into the problem of lineage specification by comparing global changes in chromatin and transcription between ES and neural stem (NS) cells, points respectively of departure and arrival for neural commitment. With these maps of the differentiated state in place, a central task is now to unravel the chromatin dynamics that enables these differentiation transitions. In particular, the observation that lineage-specific genes repressed in ES cells by Polycomb-mediated H3-K27 trimethylation (H3-K27me3) are demethylated and derepressed in differentiated cells posited the existence of a specific H3-K27 demethylase.In order to gain insight into the epigenetic transitions that enable lineage specification, we investigated the early stages of neural commitment using as model system the monolayer differentiation of mouse ES cells into neural stem (NS) cells. Starting from a comprehensive profiling of JmjC-domain genes, we report here that Jmjd3, recently identified as a H3-K27me3 specific demethylase, controls the expression of key regulators and markers of neurogenesis and is required for commitment to the neural lineage.Our results demonstrate the relevance of an enzymatic activity that antagonizes Polycomb regulation and highlight different modalities through which the dynamics of H3-K27me3 is related to transcriptional output. By showing that the H3-K27 demethylase Jmjd3 is required for commitment to the neural lineage and that it resolves the bivalent domain at the Nestin promoter, our work confirms the functional relevance of bivalent domain resolution that had been posited on the basis of the genome-wide correlation between their controlled resolution and differentiation. In addition, our data indicate that the regulation of H3-K27me3 is highly gene- and context- specific, suggesting that the interplay of methyltransferases and demethylases enables the fine-tuning more than the on/off alternation of methylation states.Thomas BurgoldFabio SpreaficoFrancesca De SantaMaria Grazia TotaroElena ProsperiniGioacchino NatoliGiuseppe TestaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e3034 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thomas Burgold Fabio Spreafico Francesca De Santa Maria Grazia Totaro Elena Prosperini Gioacchino Natoli Giuseppe Testa The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.
description	Patterns of methylation at lysine 4 and 27 of histone H3 have been associated with states of gene activation and repression that are developmentally regulated and are thought to underlie the establishment of lineage specific gene expression programs. Recent studies have provided fundamental insight into the problem of lineage specification by comparing global changes in chromatin and transcription between ES and neural stem (NS) cells, points respectively of departure and arrival for neural commitment. With these maps of the differentiated state in place, a central task is now to unravel the chromatin dynamics that enables these differentiation transitions. In particular, the observation that lineage-specific genes repressed in ES cells by Polycomb-mediated H3-K27 trimethylation (H3-K27me3) are demethylated and derepressed in differentiated cells posited the existence of a specific H3-K27 demethylase.In order to gain insight into the epigenetic transitions that enable lineage specification, we investigated the early stages of neural commitment using as model system the monolayer differentiation of mouse ES cells into neural stem (NS) cells. Starting from a comprehensive profiling of JmjC-domain genes, we report here that Jmjd3, recently identified as a H3-K27me3 specific demethylase, controls the expression of key regulators and markers of neurogenesis and is required for commitment to the neural lineage.Our results demonstrate the relevance of an enzymatic activity that antagonizes Polycomb regulation and highlight different modalities through which the dynamics of H3-K27me3 is related to transcriptional output. By showing that the H3-K27 demethylase Jmjd3 is required for commitment to the neural lineage and that it resolves the bivalent domain at the Nestin promoter, our work confirms the functional relevance of bivalent domain resolution that had been posited on the basis of the genome-wide correlation between their controlled resolution and differentiation. In addition, our data indicate that the regulation of H3-K27me3 is highly gene- and context- specific, suggesting that the interplay of methyltransferases and demethylases enables the fine-tuning more than the on/off alternation of methylation states.
format	article
author	Thomas Burgold Fabio Spreafico Francesca De Santa Maria Grazia Totaro Elena Prosperini Gioacchino Natoli Giuseppe Testa
author_facet	Thomas Burgold Fabio Spreafico Francesca De Santa Maria Grazia Totaro Elena Prosperini Gioacchino Natoli Giuseppe Testa
author_sort	Thomas Burgold
title	The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.
title_short	The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.
title_full	The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.
title_fullStr	The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.
title_full_unstemmed	The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.
title_sort	histone h3 lysine 27-specific demethylase jmjd3 is required for neural commitment.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/8431b88aec124da98c71019e648380d5
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The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment.

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