The human neuronal alpha 1-chimaerin gene contains a position-dependent negative regulatory element in the first exon.
alpha 1-Chimaerin mRNA, which encodes a neuron-specific GTPase-activating protein for the signal transduction molecule p21 Rac, is highly expressed in certain brain regions and neuronal cell lines. The promoter region of human alpha 1-chimaerin transcriptional unit contains no TATA box, Sp1-binding site or initiator motif. However, a CCAAT box located in the proximal promoter region is essential for promoter activity. We now describe a negative regulatory element in the 5' untranslated region of exon 1 of the human alpha 1-chimaerin gene. Deletion of this 70-bp region from the alpha 1-chimaerin minimal promoter increased the promoter activity 5- to 6-fold. The negative element can suppress heterologous thymidine kinase promoter activity in an orientation-independent manner when placed in its native position. However, its function is position-dependent. The presence of a putative factor in rat liver, HepG2 and SK-N-SH cell nuclear extracts but not in rat brain nuclear extract which interacts with this element suggests a possible role of the negative element in controlling the neuron-specific expression of alpha 1-chimaerin in vivo.
Glaxo-IMCB group, Institute of Molecular and Cell Biology, National University of Singapore, Singapore.
J M
JM
Dong
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Lim
D000818:Animals; D001921:Brain / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D005091:Exons; D020690:GTPase-Activating Proteins; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D013937:Thymidine Kinase / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D020690:GTPase-Activating Proteins; D011506:Proteins; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase