Examining histone acetlylation at specific genomic regions.

Abstract

The acetylation of core histones can modulate the expression of numerous genes. In general, the deacetylation of histones results in transcriptional repression, whereas increases in histone acetylation lead to the enhancement of gene transcription. Since histone acetylation is maintained during mitosis, the acetylation pattern may contribute a heritable epigenetic imprint that can continue to influence gene transcription (1). These findings suggest that the degree of histone acetylation may represent one of several nonexclusive mechanisms that can initiate or maintain the allele-specific silencing of genomic imprinting. We have recently shown that the inhibition of histone deacetylation by Trichostatin A (TSA) induces the expression of the normally imprinted maternal IGF2 allele (2), leading to biallelic expression in both human and murine cells. Partial loss of imprinting of both sense and antisense Igf2r is also observed after TSA treatment. It has also been shown that exposure of mouse conceptuses to TSA leads to loss of H19 imprinting (3). In X-chromosome inactivation, the inactive chromosome is associated with relatively underacetylated histones (4). Changes in histone acetylation become apparent after the expression of Xist, the gene responsible for X-chromosome gene silencing, and after the downregulation of the inactivated X-chromosome genes (5), suggesting that decreased histone acetylation may mark or otherwise stabilize transcriptional repression rather than actually initiate it.