Open AccessGCNF‐Dependent Activation of Cyclin D1 Expression via Repression of Mir302a During ESC Differentiation
Author(s) -
Wang Hongran,
Wang Xiaohong,
Archer Trevor K.,
Zwaka Thomas P.,
Cooney Austin J.
Publication year - 2014
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.1689
Subject(s) - biology , psychological repression , cyclin d1 , microbiology and biotechnology , expression (computer science) , cyclin , cancer research , genetics , gene expression , cell , cell cycle , gene , computer science , programming language
Cyclin D1 plays an important role in the regulation of cellular proliferation and its expression is activated during gastrulation in the mouse; however, it remains unknown how cyclin D1 expression is regulated during early embryonic development. Here, we define the role of germ cell nuclear factor ( GCNF ) in the activation of cyclin D1 expression during embryonic stem cell (ESC) differentiation as a model of early development. During our study of GCNF knockout ( GCNF − / − ) ESC, we discovered that loss of GCNF leads to the repression of cyclin D1 activation during ESC differentiation. This was determined to be an indirect effect of deregulation Mir302a, which is a cyclin D1 suppressor via binding to the 3′UTR of cyclin D1 mRNA. Moreover, we showed that Mir302 is a target gene of GCNF that inhibits Mir302 expression by binding to a DR0 element within its promoter. Inhibition of Mir302a using Mir302 inhibitor during differentiation of GCNF − / − ESCs restored cyclin D1 expression. Similarly over‐expression of GCNF during differentiation of GCNF − / − ESCs rescued the inhibition of Mir302a expression and the activation of cyclin D1. These results reveal that GCNF plays a key role in regulating activation of cyclin D1 expression via inhibition of Mir302a. S tem C ells 2014;32:1527–1537