NDLI: The Xist lncRNA directly interacts with SHARP to silence transcription through HDAC3

Content Provider	PubMed Central
Author	Mchugh, Colleen A. Chen, Chun-kan Chow, Amy Surka, Christine F. Tran, Christina Mcdonel, Patrick Amy, Pandya-jones Blanco, Mario Burghard, Christina Moradian, Annie Sweredoski, Michael J. Shishkin, Alexander A. Julia, Su Lander, Eric S. Hess, Sonja Plath, Kathrin Guttman, Mitchell
Abstract	Many long non-coding RNAs (lncRNAs) affect gene expression 1 , but the mechanisms by which they act are still largely unknown 2 . One of the best-studied lncRNAs is Xist, which is required for transcriptional silencing of one X-chromosome during development in female mammals 3,4 . Despite extensive efforts to define the mechanism of Xist-mediated transcriptional silencing, we still do not know any proteins required for this role 3 . The main challenge is that there are currently no methods to comprehensively define the proteins that directly interact with a lncRNA in the cell 5 . Here we develop a method to purify a lncRNA and identify its direct interacting proteins using quantitative mass spectrometry. We identify 10 proteins that specifically associate with Xist, three of these proteins – SHARP, SAF-A, and LBR – are required for Xist-mediated transcriptional silencing. We show that SHARP, which interacts with the SMRT co-repressor 6 that activates HDAC3 7 , is not only essential for silencing, but is also required for the exclusion of RNA Polymerase II (PolII) from the inactive X. Both SMRT and HDAC3 are also required for silencing and PolII exclusion. In addition to silencing transcription, SHARP and HDAC3 are required for Xist-mediated recruitment of the polycomb repressive complex 2 (PRC2) across the X-chromosome. Our results suggest that Xist silences transcription by directly interacting with SHARP, recruiting SMRT, activating HDAC3, and deacetylating histones to exclude PolII across the X-chromosome.
Related Links	http://dx.doi.org/10.1038/nature14443
Ending Page	236
Page Count	5
Starting Page	232
File Format	PDF
ISSN	14764687
e-ISSN	14764687
Journal	Nature
Issue Number	7551
Volume Number	521
Language	English
Publisher Date	2015-05-14
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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