Tissue- and cell-specific casein gene expression. II. Relationship to site-specific DNA methylation

M. L. Johnson, J. Levy, S. C. Supowit, L. Y. Yu-Lee, J. M. Rosen

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26 Scopus citations


The relationship between DNA methylation and the expression of the γ- and β-casein genes was investigated in both expressing and nonexpressing tissues and in isolated tumor cell subpopulations displaying differential casein gene expression. MspI/HpaII digestions of DNA isolated from liver, a totally nonexpressing tissue, indicated that specific sites of hypermethylation existed in these genes as compared to the DNA isolated from casein-producing lactating mammary gland. The positions of these sites were mapped in the γ-casein gene by comparing total genomic DNA Southern blots to the restriction digests of several overlapping phage clones constituting the γ-casein gene. In contrast, the methylation status of the HhaI sites in the γ-casein gene was found to be invariant regardless of the expression status of the gene. The inverse correlation between the hypermethylation of certain MspI/HpaII restriction sites in the casein genes and their potential expressibility was further substantiated by studies in 7,12-dimethylbenz[a]anthracene- and N-nitrosomethylurea-induced mammary carcinomas, which have an attenuated casein gene expression, and in cell subpopulations isolated from the 7,12-dimethylbenz[a]anthracene tumor which were either depleted or enriched in casein-producing cells. Analysis of total tumor DNAs indicated that the casein genes were hypermethylated at the same sites observed in liver. However, a very faint hybridization signal was observed in the HpaII digests, suggesting cell-specific methylation differences. We have confirmed the hypomethylation of at least two of these MspI/HpaII sites within the subpopulation containing the casein-producing cells at a level consistent with the relative enrichment in that fraction. These results demonstrate differential site-specific casein gene methylation not only between tissues but also between cell subpopulations within a single tissue.

Original languageEnglish
Pages (from-to)10805-10811
Number of pages7
JournalJournal of Biological Chemistry
Issue number17
StatePublished - 1 Dec 1983
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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