A member of the nuclear factor-1 family is involved in the pituitary repression of the human placental growth hormone genes

The human growth hormone (GH) gene family consists of five tandemly arrange d and highly related genes, including the chorionic somatomammotropins (CSs ), at a single locus on chromosome 17. Despite striking homologies in promo ter and flanking DNA sequences, the genes within this locus have different tissue-specific patterns of expression: GH-N is expressed almost exclusivel y in the somatotrophs of the anterior pituitary; the remaining genes, inclu ding CS-A, are expressed in placental syncytiotrophoblast. Previously we pr oposed 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 correspon ding factors (PSF-A and PSF-B). We have now examined the possibility that P SF-A and PSF-B are members of the nuclear factor (NF)-1 family. Transcripts of NF-1A, NF-IC and NF-1X, but not of NF-1B, were readily detected in GC c ells. High-affinity binding of NF-1 to PSE-B, but not to PSE-A, was confirm ed by competition of DNA-protein interactions by using NF-1 DNA elements an d 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, thi s difference was shown to be consistent with variations in NF-l-binding seq uences. These results indicate that PSF-B, but not PSF-A, is a member of th e NF-1 family, which participates in the PSF complex and in the repression of the CSA promoter in pituitary GC cells.