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RNF12 activates Xist and is essential for X chromosome inactivation.

TitleRNF12 activates Xist and is essential for X chromosome inactivation.
Publication TypeJournal Article
Year of Publication2011
AuthorsBarakat TStefan, Gunhanlar N, Pardo CGontan, Achame EMulugeta, Ghazvini M, Boers R, Kenter A, Rentmeester E, J Grootegoed A, Gribnau J
JournalPLoS Genet
Volume7
Issue1
Paginatione1002001
Date Published2011
ISSN1553-7404
KeywordsAnimals, Embryonic Stem Cells, Female, Fluorescent Antibody Technique, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Silencing, Genetic Vectors, Homeodomain Proteins, In Situ Hybridization, Fluorescence, Introns, Male, Mice, Repressor Proteins, RNA, Long Noncoding, RNA, Untranslated, Ubiquitin-Protein Ligases, X Chromosome Inactivation
Abstract

In somatic cells of female placental mammals, one of the two X chromosomes is transcriptionally silenced to accomplish an equal dose of X-encoded gene products in males and females. Initiation of random X chromosome inactivation (XCI) is thought to be regulated by X-encoded activators and autosomally encoded suppressors controlling Xist. Spreading of Xist RNA leads to silencing of the X chromosome in cis. Here, we demonstrate that the dose dependent X-encoded XCI activator RNF12/RLIM acts in trans and activates Xist. We did not find evidence for RNF12-mediated regulation of XCI through Tsix or the Xist intron 1 region, which are both known to be involved in inhibition of Xist. In addition, we found that Xist intron 1, which contains a pluripotency factor binding site, is not required for suppression of Xist in undifferentiated ES cells. Analysis of female Rnf12⁻/⁻ knockout ES cells showed that RNF12 is essential for initiation of XCI and is mainly involved in the regulation of Xist. We conclude that RNF12 is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI.

DOI10.1371/journal.pgen.1002001
Alternate JournalPLoS Genet.
PubMed ID21298085
PubMed Central IDPMC3029249
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