Subtle differences in human pregnancy-specific glycoprotein gene promoters allow for differential expression.
Eleven pregnancy-specific glycoprotein (PSG) genes reside on human chromosome 19. The sequence of these genes is extremely similar and that similarity extends to their putative control regions. However, the expression pattern of each PSG gene differs in the placenta, the primary site of PSG synthesis. To understand the molecular mechanisms underlying differential PSG expression, we characterized promoter elements of six PSG genes. We have shown previously that nucleotides -172 to -34 with respect to the translation start site constitute a minimal promoter in the PSG12 gene (class 1). We now show that PSG1-I and PSG3 are also members of class 1 genes. In contrast, only nucleotides -172 to -80 are necessary for promoter activity in PSG5, PSG6, and PSG11 genes (class 2). Class 2 genes contain a perfect Sp1 recognition sequence (CCCCGCCC) at nucleotides -148 to -141 which is necessary for promoter activity. Placental cell extracts formed three protein-DNA complexes with nucleotides -172 to -80 of all six PSG genes. One of the components of these complexes is an Sp1-like molecule. We have previously reported activator sequences within nucleotides -83 to -34 in PSG12. We now show that a 50-kDa protein binds to this region of PSG12, and the resultant complex can be supershifted by a monoclonal antibody to PEA3.
Chamberlin
M E
ME
Human Genetics Branch, NICHHD, National Institutes of Health, Bethesda, Maryland 20892.
Lei
K J
KJ
Chou
J Y
JY
D001483:Base Sequence; D002888:Chromosomes, Human, Pair 19; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D011257:Pregnancy Proteins / Q000235:genetics*; D011268:Pregnancy-Specific beta 1-Glycoproteins; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D011257:Pregnancy Proteins; D011268:Pregnancy-Specific beta 1-Glycoproteins; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C082668:pregnancy-specific beta-1-glycoprotein 12; C065788:transcription factor PEA3