rnf12 activates xist and is essential for x chromosome inactivationrnf12激活xist和x染色体失活是至关重要的.pdfVIP

RNF12 Activates Xist and Is Essential for X Chromosome Inactivation 1 1 1 1 Tahsin Stefan Barakat , Nilhan Gunhanlar , Cristina Gontan Pardo , Eskeatnaf Mulugeta Achame , 1,2 1 1 1 1 Mehrnaz Ghazvini , Ruben Boers , Annegien Kenter , Eveline Rentmeester , J. Anton Grootegoed , Joost Gribnau1* 1 Department of Reproduction and Development, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, 2 Erasmus Stem Cell Institute, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 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 Rnf122/ 2 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 indispensab