MULTIPLE PROMOTER ELEMENTS IN THE HUMAN CHORIONIC-GONADOTROPIN BETA-SUBUNIT GENES DISTINGUISH THEIR EXPRESSION FROM THE LUTEINIZING-HORMONE BETA-GENE

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:106

Article

HOLLENBERG, AN ; PESTELL, RG ; ALBANESE, C ; BOERS, ME ; JAMESON, JL

关键词: CHORIONIC GONADOTROPIN;    LUTEINIZING HORMONE;    PLACENTA;    TISSUE-SPECIFIC EXPRESSION;    GENE REGULATION;    GENE EVOLUTION;   

DOI  :  10.1016/0303-7207(94)90192-9

来源: Elsevier

【 摘 要 】

The beta subunit of human chorionic gonadotropin (CG beta) is encoded by a cluster of six genes, which have developed through gene duplication from an ancestral LH beta gene. Despite approximately 90% sequence homology between the CG beta and LH beta promoters, the CG beta gene is expressed in the placenta, whereas the LH beta promoter is active only in the pituitary. The CG beta gene uses a TATA-less promoter that is located upstream of the transcriptional start site used by the homologous LH beta gene. The purpose of this study was to use the high degree of homology among members of the CG beta gene cluster and between the CG beta and LH beta promoters to localize regulatory elements that confer CG beta expression in the placenta. The 5'-flanking regions of the different CG beta genes were cloned and expressed in JEG-3 placental cells. Naturally occurring sequence variations were correlated with promoter activity and used to identify candidate regulatory elements. Exchanges of homologous sequences in the CG beta 5 and LH beta proximal promoters identified three separate regions between -362 and +104 that are necessary for full basal expression of the CG beta promoter. Site-directed mutagenesis of four evolutionarily divergent sequences near the CG beta transcription start site confirmed the importance of multiple distinct regulatory elements as each of these mutations resulted in an 80% decrease in promoter activity. These data support a model in which placental expression of the CG beta promoter has evolved from an ancestral LH beta promoter by the accumulation of multiple, combinatorial regulatory elements rather than by acquisition of single distinct tissue-specific enhancer.

【 授权许可】

Free