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Relationship between DNA methylation, histone H4 acetylation and gene expression in the mouse imprinted Igf2‐H19 domain
Author(s) -
Grandjean Valerie,
O'Neill Laura,
Sado Takashi,
Turner Bryan,
Ferguson-Smith Anne
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02349-8
Subject(s) - histone h4 , biology , trichostatin a , acetylation , hdac4 , dna methylation , histone methylation , epigenetics of physical exercise , histone , cancer epigenetics , histone h2a , epigenetics , histone code , histone methyltransferase , microbiology and biotechnology , epigenomics , histone deacetylase , genetics , gene , gene expression , nucleosome
DNA methylation and histone H4 acetylation play a role in gene regulation by modulating the structure of the chromatin. Recently, these two epigenetic modifications have dynamically and physically been linked. Evidence suggests that both modifications are involved in regulating imprinted genes – a subset of genes whose expression depends on their parental origin. Using immunoprecipitation assays, we investigate the relationship between DNA methylation, histone H4 acetylation and gene expression in the well‐characterised imprinted Igf2‐H19 domain on mouse chromosome 7. A systematic regional analysis of the acetylation status of the domain shows that parental‐specific differences in acetylation of the core histone H4 are present in the promoter regions of both Igf2 and H19 genes, with the expressed alleles being more acetylated than the silent alleles. A correlation between DNA methylation, histone hypoacetylation and gene repression is evident only at the promoter region of the H19 gene. Treatment with trichostatin A, a specific inhibitor of histone deacetylase, reduces the expression of the active maternal H19 allele and this can be correlated with regional changes in acetylation within the upstream regulatory domain. The data suggest that histone H4 acetylation and DNA methylation have distinct functions on the maternal and paternal Igf2‐H19 domains.