Changes in gene expression and DNA methylation in adrenocortical cells senescing in culture

Peter J. Hornsby, Lianqing Yang, Satyanarayana G. Raju, Charles Y. Cheng

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Recent experiments in cultured bovine adrenocortical cells show that the previously observed phenotypic switching of CYP17 (steroid 17α-hydroxylase) expression is preceded at a much earlier time by changes in methylation in the CYP17 5′ flanking region. Two CpG sites that are methylated in the adrenal cortex in vivo were observed to undergo rapid demethylation when adrenocortical cells were places in cultured. Two adjacent CpG sites that are also methylated in vivo did not demethylate; these two sites are completely nonmethylated in fibroblasts. All CpG sites downstream, in the promoter or coding region, are always methylated in all tissues and in bovine adrenocortical cells even after many population doublings in culture. In contrast to the specific and rapid demethylation of sites in CYP17, satellite I shows a slower and apparently random loos of methylation that extends over the entire replicative life span. These changes in methylation provide examples of genetic instability in cells that undergo senescence in culture. Future experiments will focus on the relationship of these events to the phenotypic switching process.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalMutation Research DNAging
Volume256
Issue number2-6
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

Keywords

  • Adrenocortical cells
  • Methylation
  • Satellite DNA
  • Senescence
  • Steroid 17α-hydroxylase

ASJC Scopus subject areas

  • Aging
  • Molecular Biology
  • Genetics

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