MAMMARY GLAND-SPECIFIC HYPOMETHYLATION OF HPAII SITES FLANKING THE BOVINE ALPHA-S1-CASEIN GENE

In the lactating cow, mammary gland-specific hypomethylation occurs at two HpaII sites in the 5'-flanking region of the alpha S1-casein gene , and one in the 3'-region. These sites, A, B and C, are at nucleotide position -1388, -774 and +18034, respectively, relative to the major transcription start site. Site B was hypomethylated when the alpha S1- casein gene was expressed, and methylated when not expressed. In trans genic mice containing the bovine alpha S1-casein 5' and 3' regulatory elements fused to the human lactoferrin (hLF) cDNA, in some cases simi lar methylation patterns of sites A and B, as compared to the situatio n in the cow, were observed. In five mouse lines (out of the seven ana lysed) expressing the transgene in the milk, site B was hypomethylated in the mammary gland, while it was methylated in liver. In the two ot her mouse lines, no correlation was found between transgene expression and mammary gland-specific hypomethylation of site B. One of the five mouse lines with transgene expression and showing mammary-gland-speci fic hypomethylation of site B was studied in detail. In this mouse lin e, induction of transgene expression preceded hypomethylation of site B.