Helix-loop-helix transcription factors regulate Id2 gene promoter activity

Id-like helix-loop-helix (HLH) transcription factors are involved in the regulation of proliferation and differentiation of several cell types. We isolated 5′ regulatory region of mouse Id2 gene and demonstrated that it contains several E-box clusters. These E-boxes mediate stimulatory effects of basic-HLH (bHLH) transcription factors ME1, ME2, and NSCL1 on Id2 promoter activity. Co-expression of Id2 blocks the stimulatory effect of bHLH transcription factors which suggests the presence 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 that bHLH transcription factors regulate Id2 gene expression.