Stability of histone modifications across mammalian genomes: Implications for ‘epigenetic’ marking

Abstract

The combination of chromatin immunoprecipitation (ChIP) with microarray analysis (ChIP-chip) or high-throughput sequencing (ChIP-seq and ChIP-SAGE) has provided maps of a wide variety of site-specific histone modifications across mammalian genomes in various cell types. Although distinct genomic regions and functional elements have been strongly associated with specific histone modifications, an overwhelming number of combinatorial patterns have also been observed across the genome. While peaks of enrichment in ChIP-chip and ChIP-seq data may suggest stable and predictive 'landmarks' across the genomic landscape, studies from transcribed genes indicate a more dynamic model of how these data may be interpreted. In light of such studies, which show highly dynamic methylation, acetylation and phosphorylation of histone H3 during gene transcription, we consider the extent to which genome-wide maps of chromatin state could be interpreted as 'snapshots' of heterogeneous profiles deriving from dynamic modification processes. Rather than acting as static 'epigenetic' landmarks, histone modifications may function as dynamic and transient operational marks supporting specific steps in diverse processes throughout the mammalian genome.