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

First Author  Jonkers I Year  2009
Journal  Cell Volume  139
Issue  5 Pages  999-1011
PubMed ID  19945382 Mgi Jnum  J:156024
Mgi Id  MGI:4418586 Doi  10.1016/j.cell.2009.10.034
Citation  Jonkers I, et al. (2009) RNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation. Cell 139(5):999-1011
abstractText  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.
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