Open AccessOct4/Sox2-Regulated miR-302 Targets Cyclin D1 in Human Embryonic Stem Cells
Author(s) -
Deborah A. Greer Card,
Pratibha B. Hebbar,
Leping Li,
Kevin W. Trotter,
Yoshihiro Komatsu,
Yuji Mishina,
Trevor Archer
Publication year - 2008
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00359-08
Subject(s) - biology , sox2 , embryonic stem cell , microbiology and biotechnology , cyclin d1 , induced pluripotent stem cell , cell cycle , microrna , cyclin a , nanog homeobox protein , genetics , cell , gene
Oct4 and Sox2 are transcription factors required for pluripotency during early embryogenesis and for the maintenance of embryonic stem cell (ESC) identity. Functional mechanisms contributing to pluripotency are expected to be associated with genes transcriptionally activated by these factors. Here, we show that Oct4 and Sox2 bind to a conserved promoter region of miR-302, a cluster of eight microRNAs expressed specifically in ESCs and pluripotent cells. The expression of miR-302a is dependent on Oct4/Sox2 in human ESCs (hESCs), and miR-302a is expressed at the same developmental stages and in the same tissues as Oct4 during embryogenesis. miR-302a is predicted to target many cell cycle regulators, and the expression of miR-302a in primary and transformed cell lines promotes an increase in S-phase and a decrease in G1 -phase cells, reminiscent of an ESC-like cell cycle profile. Correspondingly, the inhibition of miR-302 causes hESCs to accumulate in G1 phase. Moreover, we show that miR-302a represses the productive translation of an important G1 regulator, cyclin D1, in hESCs. The transcriptional activation of miR-302 and the translational repression of its targets, such as cyclin D1, may provide a link between Oct4/Sox2 and cell cycle regulation in pluripotent cells.