Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification.

ABSTRACT: Pluripotent stem cells (PSCs) hold great clinical potential, as they possess the capacity to differentiate into fully specialised tissues such as pancreas, liver, neurons and cardiac muscle. However, the molecular mechanisms that coordinate pluripotent exit with lineage specification remain poorly understood. To address this question, we perform a small molecule screen to systematically identify novel regulators of the Smad2 signalling network, a key determinant of PSC fate. We reveal an essential function for BET family bromodomain proteins in Smad2 activation, distinct from the role of Brd4 in pluripotency maintenance. Mechanistically, BET proteins specifically engage Nodal gene regulatory elements (NREs) to promote Nodal signalling and Smad2 developmental responses. In pluripotent cells

SUBMITTER: Fernandez-Alonso R 

PROVIDER: S-EPMC5494510 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature