The role of histone acetylation in the allelic expression of the imprinted human insulin-like growth factor II gene.

Reversible histone acetylation plays a central role in X chromosome inactivation. Histones are hypoacetylated on the heavily methylated inactive X chromosome and are hyperacetylated in the unmethylated "CpG islands" in animal genomes. We have investigated whether histone acetylation is involved in the regulation of the allelic expression of insulin-like growth factor II (IGF2), a maternally imprinted gene. HSK09, a human fibroblast cell line, retained normal monoallelic expression of IGF2 in culture. When these cells were treated with histone deacetylase inhibitors, sodium butyrate or trichostatin A, biallelic expression of IGF2 was observed from all of the promoters that are expressed. These results suggest that, in addition to DNA methylation, differential histone acetylation of two parental alleles may be another potential mechanism by which the imprinting of IGF2 is regulated, probably through changes in the local chromatin structure of the imprinted locus on chromosome 11p15.