A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.

We have elucidated the kinetics of histone methylation during X inactivation using an inducible Xist expression system in mouse embryonic stem (ES) cells. Previous reports showed that the ability of Xist to trigger silencing is restricted to an early window in ES cell differentiation. Here we show t...

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Main Authors: Alexander Kohlmaier, Fabio Savarese, Monika Lachner, Joost Martens, Thomas Jenuwein, Anton Wutz
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2004-07-01
Series:PLoS Biology
Online Access:http://europepmc.org/articles/PMC449785?pdf=render
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author Alexander Kohlmaier
Fabio Savarese
Monika Lachner
Joost Martens
Thomas Jenuwein
Anton Wutz
author_facet Alexander Kohlmaier
Fabio Savarese
Monika Lachner
Joost Martens
Thomas Jenuwein
Anton Wutz
author_sort Alexander Kohlmaier
collection DOAJ
description We have elucidated the kinetics of histone methylation during X inactivation using an inducible Xist expression system in mouse embryonic stem (ES) cells. Previous reports showed that the ability of Xist to trigger silencing is restricted to an early window in ES cell differentiation. Here we show that this window is also important for establishing methylation patterns on the potential inactive X chromosome. By immunofluorescence and chromatin immunoprecipitation experiments we show that histone H3 lysine 27 trimethylation (H3K27m3) and H4 lysine 20 monomethylation (H4K20m1) are associated with Xist expression in undifferentiated ES cells and mark the initiation of X inactivation. Both marks depend on Xist RNA localisation but are independent of silencing. Induction of Xist expression after the initiation window leads to a markedly reduced ability to induce H3K27m3, whereas expression before the restrictive time point allows efficient H3K27m3 establishment. Our data show that Xist expression early in ES cell differentiation establishes a chromosomal memory, which is maintained in the absence of silencing. One consequence of this memory is the ability to introduce H3K27m3 efficiently after the restrictive time point on the chromosome that has expressed Xist early. Our results suggest that this silencing-independent chromosomal memory has important implications for the maintenance of X inactivation, where previously self-perpetuating heterochromatin structures were viewed as the principal form of memory.
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spelling doaj.art-a6db8abf1e7c4c67ba867d6f4b37109e2022-12-21T22:04:55ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852004-07-0127E17110.1371/journal.pbio.0020171A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.Alexander KohlmaierFabio SavareseMonika LachnerJoost MartensThomas JenuweinAnton WutzWe have elucidated the kinetics of histone methylation during X inactivation using an inducible Xist expression system in mouse embryonic stem (ES) cells. Previous reports showed that the ability of Xist to trigger silencing is restricted to an early window in ES cell differentiation. Here we show that this window is also important for establishing methylation patterns on the potential inactive X chromosome. By immunofluorescence and chromatin immunoprecipitation experiments we show that histone H3 lysine 27 trimethylation (H3K27m3) and H4 lysine 20 monomethylation (H4K20m1) are associated with Xist expression in undifferentiated ES cells and mark the initiation of X inactivation. Both marks depend on Xist RNA localisation but are independent of silencing. Induction of Xist expression after the initiation window leads to a markedly reduced ability to induce H3K27m3, whereas expression before the restrictive time point allows efficient H3K27m3 establishment. Our data show that Xist expression early in ES cell differentiation establishes a chromosomal memory, which is maintained in the absence of silencing. One consequence of this memory is the ability to introduce H3K27m3 efficiently after the restrictive time point on the chromosome that has expressed Xist early. Our results suggest that this silencing-independent chromosomal memory has important implications for the maintenance of X inactivation, where previously self-perpetuating heterochromatin structures were viewed as the principal form of memory.http://europepmc.org/articles/PMC449785?pdf=render
spellingShingle Alexander Kohlmaier
Fabio Savarese
Monika Lachner
Joost Martens
Thomas Jenuwein
Anton Wutz
A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.
PLoS Biology
title A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.
title_full A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.
title_fullStr A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.
title_full_unstemmed A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.
title_short A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.
title_sort chromosomal memory triggered by xist regulates histone methylation in x inactivation
url http://europepmc.org/articles/PMC449785?pdf=render
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