Oct3/4 directly regulates expression of E2F3a in mouse embryonic stem cells.
Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, have a characteristic cell cycle with truncated G1 and G2 phases. Recent findings that suppression of Oct3/4 expression results in a reduced proliferation rate of ES cells suggest the involvement of Oct3/4 in the regulation of ES cell growth, although the underlying molecular mechanism remains unclear. In the present study, we identified E2F3a as a direct target gene of Oct3/4 in ES cells. Oct3/4 directly bound to the promoter region of the E2F3a gene and positively regulated expression of E2F3a in mouse ES cells. Suppression of E2F3a activity by E2F6 overexpression led to the reduced proliferation in ES cells, which was relieved by co-expression of E2F3a. Furthermore, cell growth retardation caused by loss of Oct3/4 was rescued by E2F3a expression. These results suggest that Oct3/4 upregulates E2F3a expression to promote ES cell growth.
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Japan.
Dai
D
Kanai
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Japan.
Atsushi
A
Ueda
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Japan.
Tadayuki
T
Akagi
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Japan.
Takashi
T
Yokota
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Japan. Electronic address: hkoide@med.kanazawa-u.ac.jp.
Hiroshi
H
Koide
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D050699:E2F3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D050701:E2F6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013752:Tetracycline / Q000494:pharmacology
D050699:E2F3 Transcription Factor; D050701:E2F6 Transcription Factor; C490840:E2f3 protein, mouse; C111236:E2f6 protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D013752:Tetracycline
E2F3; Embryonic stem cells; Growth; Oct3/4