The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome

被引：768

作者：

Engreitz, Jesse M. ^{[1
,2
]}

Pandya-Jones, Amy ^{[3
,4
]}

McDonel, Patrick ^{[1
]}

Shishkin, Alexander ^{[1
]}

Sirokman, Klara ^{[1
]}

Surka, Christine ^{[1
]}

Kadri, Sabah ^{[1
]}

Xing, Jeffrey ^{[1
]}

Goren, Alon ^{[1
]}

Lander, Eric S. ^{[1
,5
,6
]}

Plath, Kathrin ^{[3
,4
]}

Guttman, Mitchell ^{[1
]}

机构：

[1] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[2] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[3] Univ Calif Los Angeles, Dept Biol Chem, Jonsson Comprehens Canc Ctr, Inst Mol Biol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA

[5] MIT, Dept Biol, Cambridge, MA 02139 USA

[6] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA

来源：

SCIENCE | 2013年 / 341卷 / 6147期

关键词：

LONG NONCODING RNAS; HISTONE H3; CHROMATIN INTERACTIONS; INACTIVATION; REVEALS; DOMAINS; METHYLATION; LOCALIZATION; ORGANIZATION; EXPRESSION;

D O I：

10.1126/science.1237973

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：

Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. We investigated the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.

引用

页码：767 / +

页数：2

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