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ConteXt of change—X inactivation and disease

Epigenetic regulation is important for stable maintenance of cell identity. For continued function of organs and tissues, illegitimate changes in cell identity must be avoided. Failure to do so can trigger tumour development and disease. How epigenetic patterns are established during cell differenti...

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Autores principales: Agrelo, Ruben, Wutz, Anton
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377189/
https://www.ncbi.nlm.nih.gov/pubmed/20043281
http://dx.doi.org/10.1002/emmm.200900053
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author Agrelo, Ruben
Wutz, Anton
author_facet Agrelo, Ruben
Wutz, Anton
author_sort Agrelo, Ruben
collection PubMed
description Epigenetic regulation is important for stable maintenance of cell identity. For continued function of organs and tissues, illegitimate changes in cell identity must be avoided. Failure to do so can trigger tumour development and disease. How epigenetic patterns are established during cell differentiation has been explored by studying model systems such as X inactivation. Mammals balance the X-linked gene dosage between the sexes by silencing of one of the two X chromosomes in females. This is initiated by expression of the non-coding X-inactive specific transcript (Xist) RNA and depends on specific cellular contexts, in which essential silencing factors are expressed. Normally X inactivation is initiated in early embryogenesis, but recent reports identified instances where Xist is expressed and can initiate gene repression. Here we describe the features that characterize the cellular permissivity to initiation of X inactivation and note that these can also occur in cancer cells and in specific haematopoietic progenitors. We propose that embryonic pathways for epigenetic regulation are re-established in adult progenitor cells and tumour cells. Understanding their reactivation will deepen our understanding of tumourigenesis and may be exploited for cancer therapy.
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spelling pubmed-33771892012-09-17 ConteXt of change—X inactivation and disease Agrelo, Ruben Wutz, Anton EMBO Mol Med Review Epigenetic regulation is important for stable maintenance of cell identity. For continued function of organs and tissues, illegitimate changes in cell identity must be avoided. Failure to do so can trigger tumour development and disease. How epigenetic patterns are established during cell differentiation has been explored by studying model systems such as X inactivation. Mammals balance the X-linked gene dosage between the sexes by silencing of one of the two X chromosomes in females. This is initiated by expression of the non-coding X-inactive specific transcript (Xist) RNA and depends on specific cellular contexts, in which essential silencing factors are expressed. Normally X inactivation is initiated in early embryogenesis, but recent reports identified instances where Xist is expressed and can initiate gene repression. Here we describe the features that characterize the cellular permissivity to initiation of X inactivation and note that these can also occur in cancer cells and in specific haematopoietic progenitors. We propose that embryonic pathways for epigenetic regulation are re-established in adult progenitor cells and tumour cells. Understanding their reactivation will deepen our understanding of tumourigenesis and may be exploited for cancer therapy. WILEY-VCH Verlag 2010-01 /pmc/articles/PMC3377189/ /pubmed/20043281 http://dx.doi.org/10.1002/emmm.200900053 Text en Copyright © 2010 EMBO Molecular Medicine
spellingShingle Review
Agrelo, Ruben
Wutz, Anton
ConteXt of change—X inactivation and disease
title ConteXt of change—X inactivation and disease
title_full ConteXt of change—X inactivation and disease
title_fullStr ConteXt of change—X inactivation and disease
title_full_unstemmed ConteXt of change—X inactivation and disease
title_short ConteXt of change—X inactivation and disease
title_sort context of change—x inactivation and disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377189/
https://www.ncbi.nlm.nih.gov/pubmed/20043281
http://dx.doi.org/10.1002/emmm.200900053
work_keys_str_mv AT agreloruben contextofchangexinactivationanddisease
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