Open AccessM i RNA ‐Mediated Regulation of the SWI/SNF Chromatin Remodeling Complex Controls Pluripotency and Endodermal Differentiation in Human ESC s
Author(s) -
Wade Staton L.,
Langer Lee F.,
Ward James M.,
Archer Trevor K.
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2084
Subject(s) - biology , chromatin remodeling , chromatin , microbiology and biotechnology , embryonic stem cell , cellular differentiation , epigenetics , microrna , induced pluripotent stem cell , bivalent chromatin , endoderm , psychological repression , genetics , gene expression , gene
MicroRNAs and chromatin remodeling complexes represent powerful epigenetic mechanisms that regulate the pluripotent state. miR‐302 is a strong inducer of pluripotency, which is characterized by a distinct chromatin architecture. This suggests that miR‐302 regulates global chromatin structure; however, a direct relationship between miR‐302 and chromatin remodelers has not been established. Here, we provide data to show that miR‐302 regulates Brg1 chromatin remodeling complex composition in human embryonic stem cells (hESCs) through direct repression of the BAF53a and BAF170 subunits. With the subsequent overexpression of BAF170 in hESCs, we show that miR‐302's inhibition of BAF170 protein levels can affect the expression of genes involved in cell proliferation. Furthermore, miR‐302‐mediated repression of BAF170 regulates pluripotency by positively influencing mesendodermal differentiation. Overexpression of BAF170 in hESCs led to biased differentiation toward the ectoderm lineage during EB formation and severely hindered directed definitive endoderm differentiation. Taken together, these data uncover a direct regulatory relationship between miR‐302 and the Brg1 chromatin remodeling complex that controls gene expression and cell fate decisions in hESCs and suggests that similar mechanisms are at play during early human development. S tem C ells 2015;33:2925—2935