Id-like helix-loop-helix (HLH) transcription factors are involved in t
he regulation of proliferation and differentiation of several cell typ
es. We isolated 5' regulatory region of mouse Id2 gene and demonstrate
d that it contains several E-box clusters. These E-boxes mediate stimu
latory effects of basic-HLH (bHLH) transcription factors ME1, ME2, and
NSCL1 on Id2 promoter activity, Co-expression of Id2 blocks the stimu
latory effect of bHLH transcription factors which suggests the presenc
e of feedback loops in Id2 transcriptional regulation, Overexpression
of NSCL1 in F9 cells blocks the downregulation of Id2 gene expression
during retinoic acid induced differentiation. Our data demonstrate tha
t bHLH transcription factors regulate Id2 gene expression.