title: RNF12 is an X-Encoded dose-dependent activator of 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.
authors: Department of Reproduction and Development, Erasmus MC, University Medical Center, 3000 CA Rotterdam, The Netherlands.
authors: Iris
authors: I
authors: Jonkers
authors: Tahsin Stefan
authors: TS
authors: Barakat
authors: Eskeatnaf Mulugeta
authors: EM
authors: Achame
authors: Kim
authors: K
authors: Monkhorst
authors: Annegien
authors: A
authors: Kenter
authors: Eveline
authors: E
authors: Rentmeester
authors: Frank
authors: F
authors: Grosveld
authors: J Anton
authors: JA
authors: Grootegoed
authors: Joost
authors: J
authors: Gribnau
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D051379:Mice; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D049951:X Chromosome Inactivation
chemical_list: D012097:Repressor Proteins; C492370:RLIM protein, human; C120758:Rlim protein, mouse; D044767:Ubiquitin-Protein Ligases