title: Mammary gland-specific hypomethylation of Hpa II sites flanking the bovine alpha S1-casein gene.
abstract: In the lactating cow, mammary gland-specific hypomethylation occurs at two Hpa II 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 transgenic mice containing the bovine alpha S1-casein 5' and 3' regulatory elements fused to the human lactoferrin (hLF) cDNA, in some cases similar methylation patterns of sites A and B, as compared to the situation in the cow, were observed. In five mouse lines (out of the seven analysed) expressing the transgene in the milk, site B was hypomethylated in the mammary gland, while it was methylated in liver. In the two other 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-specific hypomethylation of site B was studied in detail. In this mouse line, induction of transgene expression preceded hypomethylation of site B.
authors.affiliation: Pharming BV, Leiden, Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Platenburg
authors.forename: E J
authors.initials: EJ
authors.lastname: Vollebregt
authors.forename: C N
authors.initials: CN
authors.lastname: Karatzas
authors.forename: E P
authors.initials: EP
authors.lastname: Kootwijk
authors.forename: H A
authors.initials: HA
authors.lastname: De Boer
authors.forename: R
authors.initials: R
authors.lastname: Strijker
mesh_terms: D000818:Animals; D001665:Binding Sites; D002364:Caseins / Q000235:genetics* / Q000378:metabolism*; D002417:Cattle; D019175:DNA Methylation; D015257:DNA-Cytosine Methylases / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D007774:Lactation; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D015183:Restriction Mapping; D014158:Transcription, Genetic
chemical_list: D002364:Caseins; C029641:DNA modification methylase HpaII; C079006:DNA modification methylase XcyI; D015257:DNA-Cytosine Methylases