Methylation-associated transcriptional silencing of the major histocompatibility complex-linked hsp70 genes in mouse cell lines

J. J. Gorzowski, C. A. Eckerley, R. G. Halgren, A. B. Mangurten, B. Phillips*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The MHC-linked hsp70 locus consists of duplicated genes, hsp70.1 and hsp70.3, which in primary mouse embryo cells are highly heat shock-inducible. Several mouse cell lines in which hsp70 expression is not activated by heat shock have been described previously, but the basis for the deficiency has not been identified. In this study, genomic footprinting analysis has identified a common basis for the deficient response of the hsp70.1 gene to heat shock in four such cell lines, viz., the promoter is inaccessible to transcription factors, including heat shock transcription factor. Southern blot analyses reveal extensive CpG methylation of a 1.2-kilobase region spanning the hsp70.1 transcription start site and hypermethylation of the adjacent hsp70.3 gene, which is presumably also inaccessible to regulatory factors. Of four additional, randomly chosen mouse cell lines, three show no or minimal hsp70.3 heat shock responsiveness and CpG methylation of both hsp70 genes, and two of the three lines exhibit a suboptimal hsp70.1 response to heat shock as well. In all three lines, the accessibility of the hsp70.1 promoter to transcription factors is detectable but clearly diminished (relative to that in primary mouse cells). Our results suggest that the tandem hsp70 genes are concomitantly methylated and transcriptionally repressed with high frequency in cultured mouse cells.

Original languageEnglish (US)
Pages (from-to)26940-26949
Number of pages10
JournalJournal of Biological Chemistry
Volume270
Issue number45
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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