Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells.

<h4>Background</h4>The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation...

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Main Authors: Mariana de Napoles, Tatyana Nesterova, Neil Brockdorff
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-09-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000860&type=printable
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author Mariana de Napoles
Tatyana Nesterova
Neil Brockdorff
author_facet Mariana de Napoles
Tatyana Nesterova
Neil Brockdorff
author_sort Mariana de Napoles
collection DOAJ
description <h4>Background</h4>The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation occurs after primordial germ cells reach the genital ridges.<h4>Principal findings/methodology</h4>We present evidence that the epigenetic reprogramming of the inactive X-chromosome is initiated earlier than was previously thought, around the time that primordial germ cells (PGCs) migrate through the hindgut. Specifically, we find that Xist RNA expression, the primary signal for establishment of chromosome silencing, is extinguished in migrating PGCs. This is accompanied by displacement of Polycomb-group repressor proteins Eed and Suz(12), and loss of the inactive X associated histone modification, methylation of histone H3 lysine 27.<h4>Conclusions/significance</h4>We conclude that X reactivation in primordial germ cells occurs progressively, initiated by extinction of Xist RNA around the time that germ cells migrate through the hindgut to the genital ridges. The events that we observe are reminiscent of X reactivation of the paternal X chromosome in inner cell mass cells of mouse pre-implantation embryos and suggest a unified model in which execution of the pluripotency program represses Xist RNA thereby triggering progressive reversal of epigenetic silencing of the X chromosome.
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spelling doaj-art-ca9e41db053146f79879eb2a296cde0f2025-08-20T02:00:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-09-0129e86010.1371/journal.pone.0000860Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells.Mariana de NapolesTatyana NesterovaNeil Brockdorff<h4>Background</h4>The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation occurs after primordial germ cells reach the genital ridges.<h4>Principal findings/methodology</h4>We present evidence that the epigenetic reprogramming of the inactive X-chromosome is initiated earlier than was previously thought, around the time that primordial germ cells (PGCs) migrate through the hindgut. Specifically, we find that Xist RNA expression, the primary signal for establishment of chromosome silencing, is extinguished in migrating PGCs. This is accompanied by displacement of Polycomb-group repressor proteins Eed and Suz(12), and loss of the inactive X associated histone modification, methylation of histone H3 lysine 27.<h4>Conclusions/significance</h4>We conclude that X reactivation in primordial germ cells occurs progressively, initiated by extinction of Xist RNA around the time that germ cells migrate through the hindgut to the genital ridges. The events that we observe are reminiscent of X reactivation of the paternal X chromosome in inner cell mass cells of mouse pre-implantation embryos and suggest a unified model in which execution of the pluripotency program represses Xist RNA thereby triggering progressive reversal of epigenetic silencing of the X chromosome.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000860&type=printable
spellingShingle Mariana de Napoles
Tatyana Nesterova
Neil Brockdorff
Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells.
PLoS ONE
title Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells.
title_full Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells.
title_fullStr Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells.
title_full_unstemmed Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells.
title_short Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells.
title_sort early loss of xist rna expression and inactive x chromosome associated chromatin modification in developing primordial germ cells
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0000860&type=printable
work_keys_str_mv AT marianadenapoles earlylossofxistrnaexpressionandinactivexchromosomeassociatedchromatinmodificationindevelopingprimordialgermcells
AT tatyananesterova earlylossofxistrnaexpressionandinactivexchromosomeassociatedchromatinmodificationindevelopingprimordialgermcells
AT neilbrockdorff earlylossofxistrnaexpressionandinactivexchromosomeassociatedchromatinmodificationindevelopingprimordialgermcells