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A long noncoding RNA influences the choice of the X chromosome to be inactivated

X chromosome inactivation (XCI) is the process of silencing one of the X chromosomes in cells of the female mammal which ensures dosage compensation between the sexes. Although theoretically random in somatic tissues, the choice of which X chromosome is chosen to be inactivated can be biased in mice...

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Autores principales: Hierholzer, Andreas, Chureau, Corinne, Liverziani, Alessandra, Ruiz, Nerea Blanes, Cattanach, Bruce M., Young, Alexander N., Kumar, Manish, Cerase, Andrea, Avner, Phil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282422/
https://www.ncbi.nlm.nih.gov/pubmed/35787055
http://dx.doi.org/10.1073/pnas.2118182119
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author Hierholzer, Andreas
Chureau, Corinne
Liverziani, Alessandra
Ruiz, Nerea Blanes
Cattanach, Bruce M.
Young, Alexander N.
Kumar, Manish
Cerase, Andrea
Avner, Phil
author_facet Hierholzer, Andreas
Chureau, Corinne
Liverziani, Alessandra
Ruiz, Nerea Blanes
Cattanach, Bruce M.
Young, Alexander N.
Kumar, Manish
Cerase, Andrea
Avner, Phil
author_sort Hierholzer, Andreas
collection PubMed
description X chromosome inactivation (XCI) is the process of silencing one of the X chromosomes in cells of the female mammal which ensures dosage compensation between the sexes. Although theoretically random in somatic tissues, the choice of which X chromosome is chosen to be inactivated can be biased in mice by genetic element(s) associated with the so-called X-controlling element (Xce). Although the Xce was first described and genetically localized nearly 40 y ago, its mode of action remains elusive. In the approach presented here, we identify a single long noncoding RNA (lncRNA) within the Xce locus, Lppnx, which may be the driving factor in the choice of which X chromosome will be inactivated in the developing female mouse embryo. Comparing weak and strong Xce alleles we show that Lppnx modulates the expression of Xist lncRNA, one of the key factors in XCI, by controlling the occupancy of pluripotency factors at Intron1 of Xist. This effect is counteracted by enhanced binding of Rex1 in DxPas34, another key element in XCI regulating the activity of Tsix lncRNA, the main antagonist of Xist, in the strong but not in the weak Xce allele. These results suggest that the different susceptibility for XCI observed in weak and strong Xce alleles results from differential transcription factor binding of Xist Intron 1 and DxPas34, and that Lppnx represents a decisive factor in explaining the action of the Xce.
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spelling pubmed-92824222022-07-15 A long noncoding RNA influences the choice of the X chromosome to be inactivated Hierholzer, Andreas Chureau, Corinne Liverziani, Alessandra Ruiz, Nerea Blanes Cattanach, Bruce M. Young, Alexander N. Kumar, Manish Cerase, Andrea Avner, Phil Proc Natl Acad Sci U S A Biological Sciences X chromosome inactivation (XCI) is the process of silencing one of the X chromosomes in cells of the female mammal which ensures dosage compensation between the sexes. Although theoretically random in somatic tissues, the choice of which X chromosome is chosen to be inactivated can be biased in mice by genetic element(s) associated with the so-called X-controlling element (Xce). Although the Xce was first described and genetically localized nearly 40 y ago, its mode of action remains elusive. In the approach presented here, we identify a single long noncoding RNA (lncRNA) within the Xce locus, Lppnx, which may be the driving factor in the choice of which X chromosome will be inactivated in the developing female mouse embryo. Comparing weak and strong Xce alleles we show that Lppnx modulates the expression of Xist lncRNA, one of the key factors in XCI, by controlling the occupancy of pluripotency factors at Intron1 of Xist. This effect is counteracted by enhanced binding of Rex1 in DxPas34, another key element in XCI regulating the activity of Tsix lncRNA, the main antagonist of Xist, in the strong but not in the weak Xce allele. These results suggest that the different susceptibility for XCI observed in weak and strong Xce alleles results from differential transcription factor binding of Xist Intron 1 and DxPas34, and that Lppnx represents a decisive factor in explaining the action of the Xce. National Academy of Sciences 2022-07-05 2022-07-12 /pmc/articles/PMC9282422/ /pubmed/35787055 http://dx.doi.org/10.1073/pnas.2118182119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Hierholzer, Andreas
Chureau, Corinne
Liverziani, Alessandra
Ruiz, Nerea Blanes
Cattanach, Bruce M.
Young, Alexander N.
Kumar, Manish
Cerase, Andrea
Avner, Phil
A long noncoding RNA influences the choice of the X chromosome to be inactivated
title A long noncoding RNA influences the choice of the X chromosome to be inactivated
title_full A long noncoding RNA influences the choice of the X chromosome to be inactivated
title_fullStr A long noncoding RNA influences the choice of the X chromosome to be inactivated
title_full_unstemmed A long noncoding RNA influences the choice of the X chromosome to be inactivated
title_short A long noncoding RNA influences the choice of the X chromosome to be inactivated
title_sort long noncoding rna influences the choice of the x chromosome to be inactivated
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282422/
https://www.ncbi.nlm.nih.gov/pubmed/35787055
http://dx.doi.org/10.1073/pnas.2118182119
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