2013-05-23T15:30:28Z http://repub.eur.nl/oai

oai:repub.eur.nl/res/pub/22817 2012-11-14T12:37:50Z org:9824 org:9825 org:9790 org:9798 org:9755 org:9829 org:9746 access:open type:article

urn:NBN:nl:ui:15-1765/22817 2012-11-14T12:37:50 mods http://hdl.handle.net/1765/22817 hdl:1765/22817 urn:NBN:nl:ui:15-1765/22817 doi:10.1371/journal.pgen.1002001 RNF12 activates Xist and is essential for X chromosome inactivation text article http://hdl.handle.net/1765/22817 http://repub.eur.nl/res/pub/22817/publisher%27s%20version.url.txt http://repub.eur.nl/res/pub/22817/0029.pdf 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. Barakat, T.S. Barakat Tahsin Stefan aut Gunhanlar, N. Gunhanlar Nilhan aut Pardo, C. G. Pardo Cristina Gontan aut Achame, E.M. Achame E.M. aut Ghazvini, M. Ghazvini Mehrnaz aut Boers, R. Boers Ruben aut Kenter, A. Kenter Annegien aut Rentmeester, E. Rentmeester Eveline aut Grootegoed, J.A. Grootegoed Johan aut Gribnau, J.H. Gribnau Joost aut 269104844 068417799 Erasmus MC: University Medical Center Rotterdam Supporting host sht en English P L o S Genetics (Print) 1553-7390 7 1 2011-02-15 article female male controlled study mouse nonhuman cell differentiation unclassified drug protein function embryonic stem cell animal cell promoter region protein depletion down regulation binding site gene silencing gene expression regulation intron X chromosome inactivation upregulation gene inactivation transcription factor NANOG transcription initiation ubiquitin protein ligase E3 X chromosome linkage cis acting element gene regulatory network protein Rnf12 trans acting factor Erasmus University Rotterdam oai:repub.eur.nl/res/pub/22817 IR OAIPMH feed (http://repub.eur.nl/oai) 2011-03-28T08:11:41Z 2011-11-23T09:59:13Z http://purl.org/eprint/accessRights/OpenAccess http://purl.org/eprint/accessRights/OpenAccess