Different transcription factors regulate nestin gene expression during P19 cell neural differentiation and central nervous system development.
Nestin is a molecular marker for neural progenitor cells. Rat and human nestin genes possess a central nervous system-specific enhancer within their second introns. However, the transcription factors that bind to the nestin enhancer have not been fully elucidated. Here, we show that the second intron of the mouse nestin gene is sufficient to drive reporter gene expression in the developing nervous system. The core sequence of this central nervous system-specific enhancer localizes to the 3' 320-bp region. The cis-elements for Sox and POU family transcription factors and the hormone-responsive element are essential for nestin expression during embryonic carcinoma P19 cell neural differentiation and in the developing chick neural tube. Interestingly, different transcription factors bind to the nestin enhancer at different stages of P19 cell neural differentiation and central nervous system development. Sox2 and SF1 may mediate basal nestin expression in undifferentiated P19EC cells, whereas Sox2, Brn1, and Brn2 bind to the enhancer in P19 neural progenitor cells. Similarly, in vivo, Oct1 binds to the nestin enhancer in embryonic day 8.5 (E8.5) mouse embryos, and Oct1, Brn1, and Brn2 bind to this enhancer in E10.5 and E12.5 mouse embryos. Our studies therefore suggest a temporal coordination of transcription factors in determining nestin gene expression.
Jin
Zhigang
Z
Laboratory of Molecular Cell Biology and State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Liu
Li
L
Bian
Wei
W
Chen
Yongfeng
Y
Xu
Guoliang
G
Cheng
Leping
L
Jing
Naihe
N
D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002645:Chickens; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis*; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000196:embryology*; D064231:Nestin; D054259:Neural Tube / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D050811:Octamer Transcription Factor-1 / Q000378:metabolism; D050809:POU Domain Factors / Q000378:metabolism*; D051381:Rats; D020218:Response Elements / Q000502:physiology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D054339:Steroidogenic Factor 1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D050811:Octamer Transcription Factor-1; D050809:POU Domain Factors; C494166:Pou2f1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; C074066:Pou3f2 protein, mouse