A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation

被引：345

作者：

Minajigi, Anand ^{[1
,2
,3
]}

Froberg, John E. ^{[1
,2
,3
]}

Wei, Chunyao ^{[1
,2
,3
]}

Sunwoo, Hongjae ^{[1
,2
,3
]}

Kesner, Barry ^{[1
,2
,3
]}

Colognori, David ^{[1
,2
,3
]}

Lessing, Derek ^{[1
,2
,3
]}

Payer, Bernhard ^{[1
,2
,3
]}

Boukhali, Myriam ^{[4
,5
]}

Haas, Wilhelm ^{[4
,5
]}

Lee, Jeannie T. ^{[1
,2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[4] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA

[5] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

来源：

SCIENCE | 2015年 / 349卷 / 6245期

基金：

美国国家科学基金会;

关键词：

PATERNAL X-CHROMOSOME; HI-C REVEALS; INACTIVE-X; REGULATORY ELEMENTS; GENE-EXPRESSION; DIFFERENTIAL EXPRESSION; DOSAGE COMPENSATION; BINDING; GENOME; CTCF;

D O I：

10.1126/science.aab2276

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform "identification of direct RNA interacting proteins" (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors-including cohesins, condensins, topoisomerases, RNA helicases, chromatin remodelers, and modifiers-that synergistically repress Xi transcription. Inhibiting two or three interactors destabilizes silencing. Although Xist attracts some interactors, it repels architectural factors. Xist evicts cohesins from the Xi and directs an Xi-specific chromosome conformation. Upon deleting Xist, the Xi acquires the cohesin-binding and chromosomal architecture of the active X. Our study unveils many layers of Xi repression and demonstrates a central role for RNA in the topological organization of mammalian chromosomes.

引用

页数：13

共 66 条

[1] Topoisomerase-mediated chromosomal break repair: an emerging player in many games [J].