Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity.

Polycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development. Using mice with an N-ethyl-N-nitrosourea (ENU)-induced mutation in Suppressor of Zeste 12 (Suz12), a core component of Polycomb Repress...

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Autores principales:	Ian J Majewski, Marnie E Blewitt, Carolyn A de Graaf, Edward J McManus, Melanie Bahlo, Adrienne A Hilton, Craig D Hyland, Gordon K Smyth, Jason E Corbin, Donald Metcalf, Warren S Alexander, Douglas J Hilton
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a9f230968c5c46ff965d7969deb13534
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spelling	oai:doaj.org-article:a9f230968c5c46ff965d7969deb135342021-11-25T05:33:24ZPolycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity.1544-91731545-788510.1371/journal.pbio.0060093https://doaj.org/article/a9f230968c5c46ff965d7969deb135342008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18416604/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Polycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development. Using mice with an N-ethyl-N-nitrosourea (ENU)-induced mutation in Suppressor of Zeste 12 (Suz12), a core component of Polycomb Repressive Complex 2 (PRC2), we show here that loss of Suz12 function enhances hematopoietic stem cell (HSC) activity. In addition to these effects on a wild-type genetic background, mutations in Suz12 are sufficient to ameliorate the stem cell defect and thrombocytopenia present in mice that lack the thrombopoietin receptor (c-Mpl). To investigate the molecular targets of the PRC2 complex in the HSC compartment, we examined changes in global patterns of gene expression in cells deficient in Suz12. We identified a distinct set of genes that are regulated by Suz12 in hematopoietic cells, including eight genes that appear to be highly responsive to PRC2 function within this compartment. These data suggest that PRC2 is required to maintain a specific gene expression pattern in hematopoiesis that is indispensable to normal stem cell function.Ian J MajewskiMarnie E BlewittCarolyn A de GraafEdward J McManusMelanie BahloAdrienne A HiltonCraig D HylandGordon K SmythJason E CorbinDonald MetcalfWarren S AlexanderDouglas J HiltonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 6, Iss 4, p e93 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Ian J Majewski Marnie E Blewitt Carolyn A de Graaf Edward J McManus Melanie Bahlo Adrienne A Hilton Craig D Hyland Gordon K Smyth Jason E Corbin Donald Metcalf Warren S Alexander Douglas J Hilton Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity.
description	Polycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development. Using mice with an N-ethyl-N-nitrosourea (ENU)-induced mutation in Suppressor of Zeste 12 (Suz12), a core component of Polycomb Repressive Complex 2 (PRC2), we show here that loss of Suz12 function enhances hematopoietic stem cell (HSC) activity. In addition to these effects on a wild-type genetic background, mutations in Suz12 are sufficient to ameliorate the stem cell defect and thrombocytopenia present in mice that lack the thrombopoietin receptor (c-Mpl). To investigate the molecular targets of the PRC2 complex in the HSC compartment, we examined changes in global patterns of gene expression in cells deficient in Suz12. We identified a distinct set of genes that are regulated by Suz12 in hematopoietic cells, including eight genes that appear to be highly responsive to PRC2 function within this compartment. These data suggest that PRC2 is required to maintain a specific gene expression pattern in hematopoiesis that is indispensable to normal stem cell function.
format	article
author	Ian J Majewski Marnie E Blewitt Carolyn A de Graaf Edward J McManus Melanie Bahlo Adrienne A Hilton Craig D Hyland Gordon K Smyth Jason E Corbin Donald Metcalf Warren S Alexander Douglas J Hilton
author_facet	Ian J Majewski Marnie E Blewitt Carolyn A de Graaf Edward J McManus Melanie Bahlo Adrienne A Hilton Craig D Hyland Gordon K Smyth Jason E Corbin Donald Metcalf Warren S Alexander Douglas J Hilton
author_sort	Ian J Majewski
title	Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity.
title_short	Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity.
title_full	Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity.
title_fullStr	Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity.
title_full_unstemmed	Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity.
title_sort	polycomb repressive complex 2 (prc2) restricts hematopoietic stem cell activity.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/a9f230968c5c46ff965d7969deb13534
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Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity.

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