Sp1 and thyroid hormone receptor differentially activate expression of human growth hormone and chorionic somatomammotropin genes.
Activation of hGH-1 expression is mediated by the pituitary-specific transcription factor GHF-I/Pit-I which binds the 5'-flanking DNA at two sites: I (-96/-70) and II (-134/-106). Although the factor(s) which direct the placental-specific expression of hCS-1 are not known, hCS-1 sequences are transcriptionally active in pituitary cells. In the present study we examined the effects of sequence differences between hGH-1 and hCS-1 5'-flanking DNAs in determining their basal and thyroid hormone-regulated promoter activities. We showed that Sp1 is a major determinant of both hGH-1 and hCS-1 promoter activities and that in hGH-1, binding and activation by Sp1 are modulated by interference from GHF-I/Pit-1 binding at the adjacent site II sequence. A single base which differed in site II of hCS-1 greatly reduced GHF-1/Pit-1 binding and thus facilitated binding and activation by Sp1. Further differences in promoter activity of hGH-1 and hCS-1 sequences were accounted for by a thyroid hormone-responsive element between -62/-48 in the hCS-1 gene. However, induction by T3 was independent of either Sp1 or GH-1/Pit-1 binding in the site II region. These data demonstrate that a small number of base changes between hGH and hCS promoter sequences subserve a number of mechanisms which may differentially modulate the expression of hGH and hCS genes.
Tansey
W P
WP
School of Biological Sciences, University of Sydney, New South Wales, Australia.
Catanzaro
D F
DF
D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D016172:DNA Fingerprinting; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D010928:Placental Lactogen / Q000235:genetics*; D010957:Plasmids; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013963:Thyroid Hormones / Q000494:pharmacology; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D011988:Receptors, Thyroid Hormone; D016329:Sp1 Transcription Factor; D013963:Thyroid Hormones; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D013006:Growth Hormone; D010928:Placental Lactogen; D015500:Chloramphenicol O-Acetyltransferase