Ncoa3 in mouse embryonic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Vibhor Kumar
PROVIDER: E-GEOD-40193 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming.
Percharde Michelle M Lavial Fabrice F Ng Jia-Hui JH Kumar Vibhor V Tomaz Rute A RA Martin Nadine N Yeo Jia-Chi JC Gil Jesús J Prabhakar Shyam S Ng Huck-Hui HH Parker Malcolm G MG Azuara Véronique V
Genes & development 20120926 20
Embryonic stem cell (ESC) pluripotency depends on a well-characterized gene regulatory network centered on Oct4, Sox2, and Nanog. In contrast, little is known about the identity of the key coregulators and the mechanisms by which they may potentiate transcription in ESCs. Alongside core transcription factors, the orphan nuclear receptor Esrrb (estrogen-related receptor β) is vital for the maintenance of ESC identity and furthermore is uniquely associated with the basal transcription machinery. H ...[more]
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Project description:Orphan nuclear receptor Esrrb is vital in maintaining ES cells and like Oct4, Sox2 and Nanog is essential for self-renewal and pluripotency. Esrrb functions in somatic cells via LBD/AF-2-dependent coactivator recruitment to target genes. Here we show that in ES cells coactivator recruitment is similarly required and identify Ncoa3 as the Esrrb coactivator needed for activation of its target genes. Ncoa3 is essential for self-renewal and the induction of pluripotency in reprogramming, and genome-wide analysis of Ncoa3 binding reveals extensive overlap with Esrrb and pluripotency factors along with marks of active genes. Mechanistically, we show Ncoa3 is specifically required to bridge RNApol2 to Esrrb. We thus identify a new member of the ES pluripotency network and describe Esrrb and Ncoa3 as key factors linking core pluripotency factors to the general transcription machinery. ChIP experiments were carried out with chromatin prepared from E14 cells as previously described (Stock et al., 2007), using 8-10 ug primary antibody for NcoA3 and 600 ug pre-cleared chromatin per IP. Antibody for NcoA3 was from Santacruz (sc-9119) .
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