A NOVEL INITIATOR REGULATES EXPRESSION OF THE NONTISSUE-SPECIFIC HELIX-LOOP-HELIX GENE ME1

The mouse ME1 gene (HEB, REB and GE1, homologues in human, rat and chi ck, respectively) is a member of the nontissue-specific helix-loop-hel ix (HLH) gene family that includes E2A, E2-2 and Drosophila daughterle ss. We have examined the factors that control ME1 gene expression. ME1 is a single copy gene that spans greater than or equal to 150 kb of D NA and contains >10 exons. Transcription was directed by an unusual in itiator element that contained a 13 bp poly d(A) tract flanked by pali ndromic and inverted repeat sequences. Both RNase protection and prime r extension analyses mapped the ME1 transcriptional start site to the center of the 13 bp poly d(A) tract. The ME1 initiator and its proxima l sequences were required for promoter activity, supported basal level s of transcription, and contributed to cell type-specific gene express ion. Other cis-elements utilized by the TATA-less ME1 promoter include d a cluster of Sp1 response elements, E-boxes and a strong repressor. Collectively, our results suggest that the ME1 initiator and other cis -elements in the proximal promoter play an important role in regulatin g ME1 gene expression.