Cloning and expression of genes encoding human pregnancy-specific glycoproteins.
The pregnancy-specific glycoproteins (PSGs) of the human placenta and the carcinoembryonic antigens comprise a subfamily within the immunoglobulin superfamily. There may be as many as 20 different PSG genes which are predominantly expressed in the placenta. As an initial step toward understanding the control of PSG expression, we isolated and characterized two nearly identical PSG genes, PSG1 and PSG1-I. PSG1, which lacks exon 1 (5'/L), but contains exons 2 (L/N), 3 (A1), 4 (A2), and 5 (B2-C), encodes five previously identified type I transcripts, PSG1a, 1b, 1c, 1d, and 1e in a L/N-A1-A2-B2-C domain arrangement. PSG1-I, which contains a complete transcriptional unit consisting of exons 5'/L, L/N, A1, and B2-C, encodes type II PSG transcripts in a L/N-A1-B2-C domain arrangement. The predicted PSG1-I-encoded proteins share nearly complete sequence identity with the PSG1-encoded members, except the latter contain extra A domains. Amplification by polymerase chain reaction of placental or hydatidiform mole cDNA demonstrates that PSG1-I is a functional type II PSG gene. Using transient expression assays, we demonstrated that the -834/-34 region upstream of the translational start site of the PSG1-I gene contained the PSG promoter elements and the -834 to -456 region contained negative control elements. Sodium butyrate, an inducer of PSG synthesis, greatly stimulated expression of all PSG1-I-chloramphenicol acetyltransferase (CAT) fusion gene constructs. However, butyrate was at least 2-fold more effective in stimulating CAT activity of fusion genes containing upstream sequences (-834 to -576) than those containing proximal sequences (-456 to -172), suggesting two regions in the PSG1-I gene that mediate the butyrate response.
Lei
K J
KJ
Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Sartwell
A D
AD
Pan
C J
CJ
Chou
J Y
JY
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003360:Cosmids; D005091:Exons; D005260:Female; D015698:Genomic Library; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D007962:Leukocytes / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family; D015345:Oligonucleotide Probes; D010920:Placenta / Q000166:cytology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D006023:Glycoproteins; D015345:Oligonucleotide Probes; D011257:Pregnancy Proteins