caa a22 4500 445861215 CHVBK 20180317145443.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00439-011-0998-5 doi (NATIONALLICENCE)springer-10.1007/s00439-011-0998-5 The X-inactivation trans-activator Rnf12 is negatively regulated by pluripotency factors in embryonic stem cells [Elektronische Daten] [Pablo Navarro, Michael Moffat, Nicholas Mullin, Ian Chambers] X-inactivation, the molecular mechanism enabling dosage compensation in mammals, is tightly controlled during mouse early embryogenesis. In the morula, X-inactivation is imprinted with exclusive silencing of the paternally inherited X-chromosome. In contrast, in the post-implantation epiblast, X-inactivation affects randomly either the paternal or the maternal X-chromosome. The transition from imprinted to random X-inactivation takes place in the inner cell mass (ICM) of the blastocyst from which embryonic stem (ES) cells are derived. The trigger of X-inactivation, Xist, is specifically downregulated in the pluripotent cells of the ICM, thereby ensuring the reactivation of the inactive paternal X-chromosome and the transient presence of two active X-chromosomes. Moreover, Tsix, a critical cis-repressor of Xist, is upregulated in the ICM and in ES cells where it imposes a particular chromatin state at the Xist promoter that ensures the establishment of random X-inactivation upon differentiation. Recently, we have shown that key transcription factors supporting pluripotency directly repress Xist and activate Tsix and thus couple Xist/Tsix control to pluripotency. In this manuscript, we report that Rnf12, a third X-linked gene critical for the regulation of X-inactivation, is under the control of Nanog, Oct4 and Sox2, the three factors lying at the heart of the pluripotency network. We conclude that in mouse ES cells the pluripotency-associated machinery exerts an exhaustive control of X-inactivation by taking over the regulation of all three major regulators of X-inactivation: Xist, Tsix, and Rnf12. The Author(s), 2011 Navarro Pablo MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, EH9 3JQ, Edinburgh, Scotland, UK aut Moffat Michael MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, EH9 3JQ, Edinburgh, Scotland, UK aut Mullin Nicholas MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, EH9 3JQ, Edinburgh, Scotland, UK aut Chambers Ian MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, EH9 3JQ, Edinburgh, Scotland, UK aut Human Genetics Springer-Verlag 130/2(2011-08-01), 255-264 0340-6717 130:2<255 2011 130 439 https://doi.org/10.1007/s00439-011-0998-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0998-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Navarro Pablo MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, EH9 3JQ, Edinburgh, Scotland, UK aut NATIONALLICENCE 700 1- Moffat Michael MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, EH9 3JQ, Edinburgh, Scotland, UK aut NATIONALLICENCE 700 1- Mullin Nicholas MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, EH9 3JQ, Edinburgh, Scotland, UK aut NATIONALLICENCE 700 1- Chambers Ian MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, EH9 3JQ, Edinburgh, Scotland, UK aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/2(2011-08-01), 255-264 0340-6717 130:2<255 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer