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X chromosome choice occurs independently of asynchronous replication timing

In mammals, dosage compensation is achieved by X chromosome inactivation in female cells. Xist is required and sufficient for X inactivation, and Xist gene deletions result in completely skewed X inactivation. In this work, we analyzed skewing of X inactivation in mice with an Xist deletion encompas...

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Autores principales: Gribnau, Joost, Luikenhuis, Sandra, Hochedlinger, Konrad, Monkhorst, Kim, Jaenisch, Rudolf
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171734/
https://www.ncbi.nlm.nih.gov/pubmed/15668296
http://dx.doi.org/10.1083/jcb.200405117
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author Gribnau, Joost
Luikenhuis, Sandra
Hochedlinger, Konrad
Monkhorst, Kim
Jaenisch, Rudolf
author_facet Gribnau, Joost
Luikenhuis, Sandra
Hochedlinger, Konrad
Monkhorst, Kim
Jaenisch, Rudolf
author_sort Gribnau, Joost
collection PubMed
description In mammals, dosage compensation is achieved by X chromosome inactivation in female cells. Xist is required and sufficient for X inactivation, and Xist gene deletions result in completely skewed X inactivation. In this work, we analyzed skewing of X inactivation in mice with an Xist deletion encompassing sequence 5 KB upstream of the promoter through exon 3. We found that this mutation results in primary nonrandom X inactivation in which the wild-type X chromosome is always chosen for inactivation. To understand the molecular mechanisms that affect choice, we analyzed the role of replication timing in X inactivation choice. We found that the two Xist alleles and all regions tested on the X chromosome replicate asynchronously before the start of X inactivation. However, analysis of replication timing in cell lines with skewed X inactivation showed no preference for one of the two Xist alleles to replicate early in S-phase before the onset of X inactivation, indicating that asynchronous replication timing does not play a role in skewing of X inactivation.
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spelling pubmed-21717342008-03-05 X chromosome choice occurs independently of asynchronous replication timing Gribnau, Joost Luikenhuis, Sandra Hochedlinger, Konrad Monkhorst, Kim Jaenisch, Rudolf J Cell Biol Research Articles In mammals, dosage compensation is achieved by X chromosome inactivation in female cells. Xist is required and sufficient for X inactivation, and Xist gene deletions result in completely skewed X inactivation. In this work, we analyzed skewing of X inactivation in mice with an Xist deletion encompassing sequence 5 KB upstream of the promoter through exon 3. We found that this mutation results in primary nonrandom X inactivation in which the wild-type X chromosome is always chosen for inactivation. To understand the molecular mechanisms that affect choice, we analyzed the role of replication timing in X inactivation choice. We found that the two Xist alleles and all regions tested on the X chromosome replicate asynchronously before the start of X inactivation. However, analysis of replication timing in cell lines with skewed X inactivation showed no preference for one of the two Xist alleles to replicate early in S-phase before the onset of X inactivation, indicating that asynchronous replication timing does not play a role in skewing of X inactivation. The Rockefeller University Press 2005-01-31 /pmc/articles/PMC2171734/ /pubmed/15668296 http://dx.doi.org/10.1083/jcb.200405117 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Gribnau, Joost
Luikenhuis, Sandra
Hochedlinger, Konrad
Monkhorst, Kim
Jaenisch, Rudolf
X chromosome choice occurs independently of asynchronous replication timing
title X chromosome choice occurs independently of asynchronous replication timing
title_full X chromosome choice occurs independently of asynchronous replication timing
title_fullStr X chromosome choice occurs independently of asynchronous replication timing
title_full_unstemmed X chromosome choice occurs independently of asynchronous replication timing
title_short X chromosome choice occurs independently of asynchronous replication timing
title_sort x chromosome choice occurs independently of asynchronous replication timing
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171734/
https://www.ncbi.nlm.nih.gov/pubmed/15668296
http://dx.doi.org/10.1083/jcb.200405117
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