HELIX-LOOP-HELIX TRANSCRIPTION FACTORS MEDIATE ACTIVATION AND REPRESSION OF THE P75LNGFR GENE

Sequence analysis of rat and human low-affinity nerve growth factor re ceptor p75LNGFR gene promoter regions revealed a single E-box cis-acti ng element, located upstream of the major transcription start sites. D eletion analysis of the E-box sequence demonstrated that it significan tly contributes to p75LNGFR promoter activity. This E box has a dual f unction; it mediates either activation or repression of the p75LNGFR p romoter activity, depending on the interacting transcription factors. We showed that the two isoforms of the class A basic helix-loop-helix (bHLH) transcription factor ME1 (ME1a and ME1b), the murine homolog of the human HEB transcription factor, specifically repress p75LNGFR pro moter activity. This repression can be released by coexpression of the HLH Id2 transcriptional regulator. In vitro analyses demonstrated tha t ME1a forms a stable complex with the p75LNGFR E box and likely compe tes with activating E-box-binding proteins. By using ME1a-overexpressi ng PC12 cells, we showed that the endogenous p75LNGFR gene is a target of ME1a repression. Together, these data demonstrate that the p75LNGF R E hox and the interacting bHLH transcription factors are involved in the regulation of p75LNGFR gene expression. These results also show t hat class A bHLH transcription factors can repress and Id-like negativ e regulators can stimulate gene expression.