Structure and regulation of the murine gamma-casein gene

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    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 -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. (C) 2002 Elsevier Science B.V All rights reserved.

    Original languageEnglish
    Pages (from-to)101-116
    Number of pages16
    JournalBiochimica et Biophysica Acta (BBA) - Gene Structure and Expression
    Volume1579
    Issue number2-3
    Publication statusPublished - 12 Dec 2002

    Keywords

    • milk
    • gene regulation
    • prolactin
    • glucocorticoid
    • STAT5
    • mammary epithelial-cells
    • high-level expression
    • site-specific recombination
    • beta-casein
    • transgenic mice
    • transcription factor
    • binding-sites
    • glucocorticoid receptor
    • bovine alpha(S1)-casein
    • distal enhancer

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