The bHLH transcription factor Hand2 regulates the expression of nanog in ANS differentiation.
The basic helix-loop-helix transcription factor Hand2 is induced by bone morphogenetic proteins (BMPs) in neural crest-derived precursor cells during the early stage of development of the autonomic nervous system (ANS). Previous studies showed that Hand2 was essential for the ANS differentiation. However, regulatory mechanism of pluripotent genes has not been elucidated in ANS differentiation. Here, we show that Hand2 regulated nanog expression in ANS differentiation. Our studies demonstrated that the forced expression of Hand2 promoted the ANS differentiation program in P19 embryonal carcinoma (EC) cells without aggregation. Furthermore, our results suggested that Hand2 bound to the promoter of nanog, a gene required for embryonic stem cells self-renewal, and suppressed nanog expression after Hand2 induction. The rapid downregulation of nanog mRNA during ANS differentiation correlated with the Hand2 transcriptional activity and nanog promoter methylation. These findings are evidence for a presence of the novel regulatory mechanism of nanog in ANS differentiation.
Laboratory of Genome Biology, Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
Yusuke
Y
Hashimoto
Reiko
R
Myojin
Naohiro
N
Katoh
Masaya
M
Ohtsu
Fumio
F
Tashiro
Fumitoshi
F
Onoda
Yasufumi
Y
Murakami
D000818:Animals; D001341:Autonomic Nervous System / Q000166:cytology / Q000254:growth & development*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D000071317:Nanog Homeobox Protein; D055495:Neurogenesis / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C498766:Hand2 protein, mouse; C475540:Nanog protein, mouse