Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells.
The pluripotency of embryonic stem (ES) cells is thought to be maintained by a few key transcription factors, including Oct3/4 and Sox2. The function of Oct3/4 in ES cells has been extensively characterized, but that of Sox2 has yet to be determined. Sox2 can act synergistically with Oct3/4 in vitro to activate Oct-Sox enhancers, which regulate the expression of pluripotent stem cell-specific genes, including Nanog, Oct3/4 and Sox2 itself. These findings suggest that Sox2 is required by ES cells for its Oct-Sox enhancer activity. Using inducible Sox2-null mouse ES cells, we show that Sox2 is dispensable for the activation of these Oct-Sox enhancers. In contrast, we demonstrate that Sox2 is necessary for regulating multiple transcription factors that affect Oct3/4 expression and that the forced expression of Oct3/4 rescues the pluripotency of Sox2-null ES cells. These results indicate that the essential function of Sox2 is to stabilize ES cells in a pluripotent state by maintaining the requisite level of Oct3/4 expression.
Masui
Shinji
S
Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Minatojima-minamimachi 2-2-3, Chu-o-ku, Kobe, Hyogo 650-0047, Japan. masui@ri.imcj.go.jp
Nakatake
Yuhki
Y
Toyooka
Yayoi
Y
Shimosato
Daisuke
D
Yagi
Rika
R
Takahashi
Kazue
K
Okochi
Hitoshi
H
Okuda
Akihiko
A
Matoba
Ryo
R
Sharov
Alexei A
AA
Ko
Minoru S H
MS
Niwa
Hitoshi
H
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development / Q000502:physiology; D053595:Embryonic Stem Cells / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D000099254:Organic Cation Transporter 3
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D027701:Organic Cation Transport Proteins; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000099254:Organic Cation Transporter 3; C475540:Nanog protein, mouse; C494174:Pou5f1 protein, mouse; C527783:Sox2 protein, mouse