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RNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation.

TitleRNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation.
Publication TypeJournal Article
Year of Publication2009
AuthorsJonkers I, Barakat TStefan, Achame EMulugeta, Monkhorst K, Kenter A, Rentmeester E, Grosveld F, J Grootegoed A, Gribnau J
JournalCell
Volume139
Issue5
Pagination999-1011
Date Published2009 Nov 25
ISSN1097-4172
KeywordsAnimals, Embryo, Mammalian, Female, Gene Expression Regulation, Developmental, Humans, Male, Mice, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Ubiquitin-Protein Ligases, X Chromosome Inactivation
Abstract

In somatic cells of female placental mammals, one X chromosome is inactivated to minimize sex-related dosage differences of X-encoded genes. Random X chromosome inactivation (XCI) in the embryo is a stochastic process, in which each X has an independent probability to initiate XCI, triggered by the nuclear concentration of one or more X-encoded XCI-activators. Here, we identify the E3 ubiquitin ligase RNF12 as an important XCI-activator. Additional copies of mouse Rnf12 or human RNF12 result in initiation of XCI in male mouse ES cells and on both X chromosomes in a substantial percentage of female mouse ES cells. This activity is dependent on an intact open reading frame of Rnf12 and correlates with the transgenic expression level of RNF12. Initiation of XCI is markedly reduced in differentiating female heterozygous Rnf12(+/-) ES cells. These findings provide evidence for a dose-dependent role of RNF12 in the XCI counting and initiation process.

DOI10.1016/j.cell.2009.10.034
Alternate JournalCell
PubMed ID19945382
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