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

被引：45

作者：

Galupa, Rafael ^{[1
,12
]}

Nora, Elphege Pierre ^{[1
,14
,15
]}

Worsley-Hunt, Rebecca ^{[2
]}

Picard, Christel ^{[1
]}

Gard, Chris ^{[1
]}

van Bemmel, Joke Gerarda ^{[1
,13
]}

Servant, Nicolas ^{[3
,4
]}

Zhan, Yinxiu ^{[5
,6
]}

El Marjou, Fatima ^{[7
]}

Johanneau, Colin ^{[7
]}

Diabangouaya, Patricia ^{[1
]}

Le Saux, Agnes ^{[1
]}

Lameiras, Sonia ^{[8
]}

da Fonseca, Juliana Pipoli ^{[8
]}

Loos, Friedemann ^{[9
]}

Gribnau, Joost ^{[9
]}

Baulande, Sylvain ^{[8
]}

Ohler, Uwe ^{[2
,10
]}

Giorgetti, Luca ^{[5
]}

Heard, Edith ^{[1
,11
,12
]}

机构：

[1] PSL Res Univ, Inst Curie, CNRS,Genet & Dev Biol Unit, UMR3215,INSERM,U934,Mammalian Dev Epigenet Grp, Paris, France

[2] Berlin Inst Med Syst Biol, Max Delbruck Ctr Mol Med, Helmholtz Assoc, Berlin, Germany

[3] PSL Res Univ, Bioinformat Biostat Epidemiol & Computat Syst Uni, INSERM, U900,Inst Curie, Paris, France

[4] PSL Res Univ, Ctr Computat Biol CBIO, MINES ParisTech, Paris, France

[5] Friedrich Miescher Inst Biomed Res, Basel, Switzerland

[6] Univ Basel, Basel, Switzerland

[7] Inst Curie, Transgenesis Facil, Paris, France

[8] Inst Curie, Inst Curie Genom Excellence ICGex, Paris, France

[9] Erasmus MC, Univ Med Ctr, Dept Dev Biol, Rotterdam, Netherlands

[10] Humboldt Univ, Dept Biol, Berlin, Germany

[11] Coll France, Paris, France

[12] European Mol Biol Lab, Heidelberg, Germany

[13] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA

[14] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA

[15] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA USA

来源：

MOLECULAR CELL | 2020年 / 77卷 / 02期

基金：

欧洲研究理事会;

关键词：

X-CHROMOSOME INACTIVATION; GENE-EXPRESSION; TRANSCRIPTIONAL REPRESSION; TSIX TRANSCRIPTION; CHROMATIN; ELEMENTS; SILENCER; ENHANCER; MOUSE; REVEALS;

D O I：

10.1016/j.molcel.2019.10.030

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页码：352 / +

页数：24

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