Relationship between DNA methylation, histone H4 acetylation and gene expression in the mouse imprinted Igf2-H19 domain

DNA methylation and histone H4 acetylation play a role in gene regulation b y modulating the structure of the chromatin, Recently, these two epigenetic modifications have dynamically and physically been linked. Evidence sugges ts that both modifications are involved in regulating imprinted genes - a s ubset of genes whose expression depends on their parental origin. Using imm unoprecipitation assays, we investigate the relationship between DNA methyl ation, histone H4 acetylation and gene expression in the well-characterised imprinted Igf2-H19 domain on mouse chromosome 7, A systematic regional ana lysis of the acetylation status of the domain shows that parental-specific differences in acetylation of the core histone H4 are present in the promot er regions of both lgf2 and H19 genes, with the expressed alleles being mor e acetylated than the silent alleles, A correlation between DNA methylation , histone hypoacetylation and gene repression is evident only at the promot er region of the H19 gene. Treatment with trichostatin A, a specific inhibi tor of histone deacetylase, reduces the expression of the active maternal H 19 allele and this can be correlated with regional changes in acetylation w ithin the upstream regulatory domain. The data suggest that histone H4 acet ylation and DNA methylation have distinct functions on the maternal and pat ernal Igf2-H19 domains. (C) 2001 Federation of European Biochemical Societi es. Published by Elsevier Science B.V.. All rights reserved.