Deletion of an X-inactivation boundary disrupts adjacent gene silencing.

In mammalian females, genes on one X are largely silenced by X-chromosome inactivation (XCI), although some "escape" XCI and are expressed from both Xs. Escapees can closely juxtapose X-inactivated genes and provide a tractable model for assessing boundary function at epigenetically regula...

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Autores principales:	Lindsay M Horvath, Nan Li, Laura Carrel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/43484e33421944ab9611d15f2d77ef27
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spelling	oai:doaj.org-article:43484e33421944ab9611d15f2d77ef272021-11-18T06:21:32ZDeletion of an X-inactivation boundary disrupts adjacent gene silencing.1553-73901553-740410.1371/journal.pgen.1003952https://doaj.org/article/43484e33421944ab9611d15f2d77ef272013-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278033/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404In mammalian females, genes on one X are largely silenced by X-chromosome inactivation (XCI), although some "escape" XCI and are expressed from both Xs. Escapees can closely juxtapose X-inactivated genes and provide a tractable model for assessing boundary function at epigenetically regulated loci. To delimit sequences at an XCI boundary, we examined female mouse embryonic stem cells carrying X-linked BAC transgenes derived from an endogenous escape locus. Previously we determined that large BACs carrying escapee Kdm5c and flanking X-inactivated transcripts are properly regulated. Here we identify two lines with truncated BACs that partially and completely delete the distal Kdm5c XCI boundary. This boundary is not required for escape, since despite integrating into regions that are normally X inactivated, transgenic Kdm5c escapes XCI, as determined by RNA FISH and by structurally adopting an active conformation that facilitates long-range preferential association with other escapees. Yet, XCI regulation is disrupted in the transgene fully lacking the distal boundary; integration site genes up to 350 kb downstream of the transgene now inappropriately escape XCI. Altogether, these results reveal two genetically separable XCI regulatory activities at Kdm5c. XCI escape is driven by a dominant element(s) retained in the shortest transgene that therefore lies within or upstream of the Kdm5c locus. Additionally, the distal XCI boundary normally plays an essential role in preventing nearby genes from escaping XCI.Lindsay M HorvathNan LiLaura CarrelPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 11, p e1003952 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Lindsay M Horvath Nan Li Laura Carrel Deletion of an X-inactivation boundary disrupts adjacent gene silencing.
description	In mammalian females, genes on one X are largely silenced by X-chromosome inactivation (XCI), although some "escape" XCI and are expressed from both Xs. Escapees can closely juxtapose X-inactivated genes and provide a tractable model for assessing boundary function at epigenetically regulated loci. To delimit sequences at an XCI boundary, we examined female mouse embryonic stem cells carrying X-linked BAC transgenes derived from an endogenous escape locus. Previously we determined that large BACs carrying escapee Kdm5c and flanking X-inactivated transcripts are properly regulated. Here we identify two lines with truncated BACs that partially and completely delete the distal Kdm5c XCI boundary. This boundary is not required for escape, since despite integrating into regions that are normally X inactivated, transgenic Kdm5c escapes XCI, as determined by RNA FISH and by structurally adopting an active conformation that facilitates long-range preferential association with other escapees. Yet, XCI regulation is disrupted in the transgene fully lacking the distal boundary; integration site genes up to 350 kb downstream of the transgene now inappropriately escape XCI. Altogether, these results reveal two genetically separable XCI regulatory activities at Kdm5c. XCI escape is driven by a dominant element(s) retained in the shortest transgene that therefore lies within or upstream of the Kdm5c locus. Additionally, the distal XCI boundary normally plays an essential role in preventing nearby genes from escaping XCI.
format	article
author	Lindsay M Horvath Nan Li Laura Carrel
author_facet	Lindsay M Horvath Nan Li Laura Carrel
author_sort	Lindsay M Horvath
title	Deletion of an X-inactivation boundary disrupts adjacent gene silencing.
title_short	Deletion of an X-inactivation boundary disrupts adjacent gene silencing.
title_full	Deletion of an X-inactivation boundary disrupts adjacent gene silencing.
title_fullStr	Deletion of an X-inactivation boundary disrupts adjacent gene silencing.
title_full_unstemmed	Deletion of an X-inactivation boundary disrupts adjacent gene silencing.
title_sort	deletion of an x-inactivation boundary disrupts adjacent gene silencing.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/43484e33421944ab9611d15f2d77ef27
work_keys_str_mv	AT lindsaymhorvath deletionofanxinactivationboundarydisruptsadjacentgenesilencing AT nanli deletionofanxinactivationboundarydisruptsadjacentgenesilencing AT lauracarrel deletionofanxinactivationboundarydisruptsadjacentgenesilencing
_version_	1718424473284116480

Deletion of an X-inactivation boundary disrupts adjacent gene silencing.

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