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 language | English |
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Pages (from-to) | 101-116 |
Number of pages | 16 |
Journal | Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression |
Volume | 1579 |
Issue number | 2-3 |
Publication status | Published - 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