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Role for Med12 in regulation of Nanog and Nanog target genes

Tutter, Antonin and Kowalski, Michael and Baltus, Gretchen and Iourgenko, Vadim and Labow, Mark and Li, En and Kadam, Shilpa (2009) Role for Med12 in regulation of Nanog and Nanog target genes. Journal of Biological Chemistry, 284 (6). pp. 3709-3718. ISSN 0021-9258

Abstract

Nanog, Oct4, and Sox2 form the core of a transcription factor network that maintains embryonic stem cells in the pluripotent state in both humans and mice. These critical factors have been implicated as both positive and negative regulators of transcription, varying by promoter and differentiation state of the cell. The Mediator complex, a ubiquitous conserved complex of approximately 30 subunits, facilitates transcription by coordinating RNA polymerase II binding to target promoters via gene-specific activators and can be divided into several functional subcomplexes. Med12 is part of a subcomplex of four proteins associated with the core Mediator complex and has been found to function both in repressing and activating transcription when recruited to target promoters. We identified an interaction between Med12 and Nanog and present evidence of involvement of Med12 in regulation of Nanog function. Gene expression analysis of embryonic stem cells knocked down for Med12 showed a similarity to Nanog knockdown, with increased expression of Nanog-repressed targets and decreased expression of Nanog-activated targets. Using chromatin immunoprecipitation, we found that Med12 and Nanog co-occupied Nanog target promoters in embryonic stem cells and that Med12 dissociated from target promoters upon differentiation with kinetics similar to Nanog. Our results indicate that Nanog and Med12 function in concert to regulate Nanog target genes and identify a novel role for Med12 in embryonic stem cell regulation.

Item Type: Article
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Additional Information: Author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
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Date Deposited: 22 Feb 2010 11:50
Last Modified: 31 Jan 2013 00:51
URI: https://oak.novartis.com/id/eprint/1700

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