Characterization of human epigenomes

Abstract

Histone modifications play a key role in regulating transcription and thus ultimately regulate cellular development and differentiation. To understand how histone modifications influence normal development and disease states, a global catalogue of histone modifications and modifying enzymes in normal and disease states is necessary. The first such systematic mapping experiments using the recently developed ChIP-Sequencing technique have revealed a combinatorial modification 'backbone' consisting of multiple histone modifications associated with active transcription. The human epigenomic datasets that are now being produced provide valuable resources for a better understanding of the functional regulatory elements of transcription and the pathways necessary for normal cellular development and pathological conditions.

Figure 1

Five scenarios for generation of co-existence of the active mark H3K4me3 and repressive mark H3K27me3. All scenarios except for the imprinted locus indicated in left panel of (b) can subject to dynamic regulation by the opposing histone methyl transferases and demethylases.

Figure 2

(A) Active gene promoters are characterized by having active modification marks both surrounding and downstream of the TSSs. (B) Promoters of inactive genes usually do not have active marks downstream of TSSs even though they may be associated with several active marks including H3K4 methylation, H3K9ac and H2A.Z in the immediately region surrounding the TSSs. Repressive marks including H3K9me2, H3K9me3, H3K27me2, H3K27me3 and H4K20me3 can be detected in inactive genes.