A Conserved Noncoding Locus Regulates Random Monoallelic Xist Expression across a Topological Boundary

作     者：Galupa, Rafael Nora, Elphege Pierre Worsley-Hunt, Rebecca Picard, Christel Gard, Chris van Bemmel, Joke Gerarda Servant, Nicolas Zhan, Yinxiu El Marjou, Fatima Johanneau, Colin Diabangouaya, Patricia Le Saux, Agnes Lameiras, Sonia da Fonseca, Juliana Pipoli Loos, Friedemann Gribnau, Joost Baulande, Sylvain Ohler, Uwe Giorgetti, Luca Heard, Edith 

作者机构：PSL Res Univ Inst Curie CNRSGenet & Dev Biol Unit UMR3215INSERMU934Mammalian Dev Epigenet Grp Paris France Berlin Inst Med Syst Biol Max Delbruck Ctr Mol Med Helmholtz Assoc Berlin Germany PSL Res Univ Bioinformat Biostat Epidemiol & Computat Syst Uni INSERM U900Inst Curie Paris France PSL Res Univ Ctr Computat Biol CBIO MINES ParisTech Paris France Friedrich Miescher Inst Biomed Res Basel Switzerland Univ Basel Basel Switzerland Inst Curie Transgenesis Facil Paris France Inst Curie Inst Curie Genom Excellence ICGex Paris France Erasmus MC Univ Med Ctr Dept Dev Biol Rotterdam Netherlands Humboldt Univ Dept Biol Berlin Germany Coll France Paris France European Mol Biol Lab Heidelberg Germany Gladstone Inst Cardiovasc Dis San Francisco CA USA Univ Calif San Francisco Cardiovasc Res Inst San Francisco CA 94143 USA Univ Calif San Francisco Dept Biochem & Biophys San Francisco CA USA 

出 版 物：《MOLECULAR CELL》 (分子细胞)

年 卷 期：2020年第77卷第2期

页      面：352-+页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：Region Ile-de-France (DIM Biotherapies) Fondation pour la Recherche Medicale [FDT20160435295] NWO-ALW Rubicon fellowship [825.13.002] NWO-ALW Veni fellowship [863.15.016] ERC Advanced Investigator award (ERC-2014-AdG) Labelisation La Ligue, FRM [DEI20151234398] ANR DoseX 2017, Labex DEEP part of the IDEX PSL [ANR-11-LBX-0044, ANR-10IDEX-0001-02 PSL] ABS4NGS [ANR-11-BINF-0001] ANR ("Investissements d'Avenir'' program) [ANR-10-EQPX-03, ANR-10-INBS-09-08] Canceropole Ile-de-France SiRIC-Curie program (SiRIC) [INCa-DGOS-4654] European Research Council (ERC) Funding Source: European Research Council (ERC) 

主　　题：TADs X-inactivation cis-regulatory landscape gene regulation noncoding RNA silencer enhancer Xist Linx 5C 

摘      要：cis-Regulatory communication is crucial in mammalian development and is thought to be restricted by the spatial partitioning of the genome in topologically associating domains (TADs). Here, we discovered that the Xist locus is regulated by sequences in the neighboring TAD. In particular, the promoter of the noncoding RNA Linx (LinxP) acts as a long-range silencer and influences the choice of X chromosome to be inactivated. This is independent of Linx transcription and independent of any effect on Tsix, the antisense regulator of Xist that shares the same TAD as Linx. Unlike Tsix, LinxP is well conserved across mammals, suggesting an ancestral mechanism for random monoallelic Xist regulation. When introduced in the same TAD as Xist, LinxP switches from a silencer to an enhancer. Our study uncovers an unsuspected regulatory axis for X chromosome inactivation and a class of cis-regulatory effects that may exploit TAD partitioning to modulate developmental decisions.