The dyskerin ribonucleoprotein complex as an OCT4/SOX2 coactivator in embryonic stem cells

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Cite this article as: eLife 2014;3:e03573 doi: 10.7554/eLife.03573

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Abstract

Acquisition of pluripotency is driven largely at the transcriptional level by activators OCT4, SOX2, and NANOG that must in turn cooperate with diverse coactivators to execute stem cell-specific gene expression programs. Using a biochemically defined in vitro transcription system that mediates OCT4/SOX2 and coactivator-dependent transcription of the Nanog gene, we report the purification and identification of the dyskerin (DKC1) ribonucleoprotein complex as an OCT4/SOX2 coactivator whose activity appears to be modulated by a subset of associated small nucleolar RNAs (snoRNAs). The DKC1 complex occupies enhancers and regulates the expression of key pluripotency genes critical for self-renewal in embryonic stem (ES) cells. Depletion of DKC1 in fibroblasts significantly decreased the efficiency of induced pluripotent stem (iPS) cell generation. This study thus reveals an unanticipated transcriptional role of the DKC1 complex in stem cell maintenance and somatic cell reprogramming.

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Yick W Fong

Brigham and Women's Hospital, Cambridge, United States

Competing interests
No competing interests declared.
Jaclyn J Ho

Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Carla Inouye

Howard Hughes Medicial Institute, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Robert Tjian

Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States

For correspondence
tjianr@hhmi.org

Competing interests
Robert Tjian, Robert Tjian is President of the Howard Hughes Medical Institute (2009-present), one of the three founding funders of eLife, and a member of eLife's Board of Directors.

Reviewing Editor

Benjamin J Blencowe, University of Toronto, Canada

Publication history

Received: June 4, 2014
Accepted: November 19, 2014
Accepted Manuscript published: November 19, 2014 (version 1)
Version of Record published: December 10, 2014 (version 2)

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.