title: A member of the nuclear factor-1 family is involved in the pituitary repression of the human placental growth hormone genes.
abstract: The human growth hormone (GH) gene family consists of five tandemly arranged and highly related genes, including the chorionic somatomammotropins (CSs), at a single locus on chromosome 17. Despite striking homologies in promoter and flanking DNA sequences, the genes within this locus have different tissue-specific patterns of expression: GH-N is expressed almost exclusively in the somatotrophs of the anterior pituitary; the remaining genes, including CS-A, are expressed in placental syncytiotrophoblast. Previously we proposed that active repression of the placental gene promoters in pituitary GC cells is mediated by upstream 'P' sequences and, specifically, a 263 bp region containing two 'P' sequence elements (PSE-A and PSE-B) and corresponding factors (PSF-A and PSF-B). We have now examined the possibility that PSF-A and PSF-B are members of the nuclear factor (NF)-1 family. Transcripts of NF-1A, NF-1C and NF-1X, but not of NF-1B, were readily detected in GC cells. High-affinity binding of NF-1 to PSE-B, but not to PSE-A, was confirmed by competition of DNA-protein interactions by using NF-1 DNA elements and antibodies. Functionally, a NF-1 element was able to substitute for PSE-B as a promoter-specific repressor in GC cells after gene transfer. However, there was a difference in the magnitude of repression exerted by the NF-1 and PSF-B elements on the CS-A promoter and, with the use of mutations, this difference was shown to be consistent with variations in NF-1-binding sequences. These results indicate that PSF-B, but not PSF-A, is a member of the NF-1 family, which participates in the PSF complex and in the repression of the CS-A promoter in pituitary GC cells.
authors.affiliation: Gene Technology Group and Department of Physiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada R3E 3J7.
authors.forename: L D
authors.initials: LD
authors.lastname: Norquay
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.forename: R M
authors.initials: RM
authors.lastname: Surabhi
authors.forename: R D
authors.initials: RD
authors.lastname: Gietz
authors.forename: N
authors.initials: N
authors.lastname: Tanese
authors.forename: P A
authors.initials: PA
authors.lastname: Cattini
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D016384:Consensus Sequence; D004268:DNA-Binding Proteins; D003850:Deoxyribonuclease I / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D010902:Pituitary Gland / Q000502:physiology*; D010926:Placental Hormones / Q000096:biosynthesis* / Q000235:genetics*; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C064980:GH2 protein, human; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D010926:Placental Hormones; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C486169:Ybx1 protein, rat; D013006:Growth Hormone; D003850:Deoxyribonuclease I