title: Structure and regulation of the murine gamma-casein gene.
abstract: The murine casein locus consists of five genes, which are coordinately regulated during mammary development. The levels of casein-specific mRNAs in mammary epithelial cells increase during the second half of pregnancy and remain high during lactation. The murine gamma-casein gene, which corresponds to the alphaS2-casein gene in ruminants, was isolated from a mouse bacterial artificial chromosome (BAC) library (strain 129SV). The gene contains 14 exons, which are distributed over 14 kb of DNA sequence. The expression pattern of the murine gamma-casein gene mimics that of the neighbouring beta-casein gene in terms of developmental induction in vivo. In cell culture, both the beta- and gamma-casein promoter are synergistically induced by prolactin and glucocorticoids. Glucocorticoid induction is critically dependent on prolactin-mediated activation of STAT5 in both promoters. Several consensus STAT5 binding sites were identified in the gamma-casein promoter, some of which may have an additive effect on prolactin induction. mRNA levels of gamma- and beta-casein are similar in lactating mammary tissue. However, promoter segments derived from the gamma-casein gene are significantly less active in cell culture than comparable fragments of the beta-casein promoter. Promoter hybrids between the gamma- and beta-casein promoters revealed that the critical sequences which are responsible for the different in vitro activity are located in a short promoter proximal region.
authors.affiliation: Molecular Recognition Group, Hannah Research Institute, Scotland, Ayr, UK. kolba@hri.sari.ac.uk
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Kolb
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002364:Caseins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D002460:Cell Line; D016384:Consensus Sequence / Q000235:genetics; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007774:Lactation; D008156:Luciferases / Q000235:genetics; D008321:Mammary Glands, Animal / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D008894:Milk Proteins; D008969:Molecular Sequence Data; D011388:Prolactin / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000235:genetics; D050799:STAT5 Transcription Factor; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
chemical_list: D002364:Caseins; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D008894:Milk Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011388:Prolactin; D004247:DNA; D008156:Luciferases