Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation

被引：35

作者：

Carter, Ava C. ^{[1
]}

Xu, Jin ^{[1
]}

Nakamoto, Meagan Y. ^{[2
]}

Wei, Yuning ^{[1
]}

Zarnegar, Brian J. ^{[3
]}

Shi, Quanming ^{[1
]}

Broughton, James P. ^{[1
]}

Ransom, Ryan C. ^{[4
]}

Salhotra, Ankit ^{[4
]}

Nagaraja, Surya D. ^{[5
]}

Li, Rui ^{[1
]}

Dou, Diana R. ^{[1
]}

Yost, Kathryn E. ^{[1
]}

Cho, Seung-Woo ^{[1
]}

Mistry, Anil ^{[6
]}

Longaker, Michael T. ^{[4
,5
]}

Khavari, Paul A. ^{[3
]}

Batey, Robert T. ^{[2
]}

Wuttke, Deborah S. ^{[2
]}

Chang, Howard Y. ^{[1
,3
,7
]}

机构：

[1] Stanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA

[2] Univ Colorado, Dept Biochem, Boulder, CO 80309 USA

[3] Stanford Univ, Dept Dermatol, Sch Med, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Surg, Div Plast & Reconstruct Surg, Sch Med, Stanford, CA 94305 USA

[5] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[6] Novartis Inst Biomed Res, Cambridge, MA USA

[7] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA

来源：

ELIFE | 2020年 / 9卷

关键词：

TRANSPOSABLE ELEMENTS; LIVING CELLS; TRANSCRIPTION; CHROMATIN; PROTEINS; REVEALS; SHARP; GENE; VISUALIZATION; GENERATION;

D O I：

10.7554/eLife.54508

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Xist lncRNA mediates X chromosome inactivation (XCI). Here we show that Spen, an Xist-binding repressor protein essential for XCI , binds to ancient retroviral RNA, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci. Spen loss activates a subset of endogenous retroviral (ERV) elements in mouse embryonic stem cells, with gain of chromatin accessibility, active histone modifications, and ERV RNA transcription. Spen binds directly to ERV RNAs that show structural similarity to the A-repeat of Xist, a region critical for Xist-mediated gene silencing. ERV RNA and Xist A-repeat bind the RRM domains of Spen in a competitive manner. Insertion of an ERV into an A-repeat deficient Xist rescues binding of Xist RNA to Spen and results in strictly local gene silencing in cis. These results suggest that Xist may coopt transposable element RNA-protein interactions to repurpose powerful antiviral chromatin silencing machinery for sex chromosome dosage compensation.

引用

页码：1 / 58

页数：27

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