Genome-wide Analyses of Histone Modifications in the Mammalian Genome

Histones undergo multiple posttranslational modifications that interact with other epigenetic layers to regulate cellular processes. Recent studies have identified several novel histone modifications, including acylation, homocysteinylation, monoaminylation, and O-GlcNAcylation, which are implicated in transcription activation. Further, at least six histone modifications have been included in ChIP-seq profiling across hundreds of biosamples in human and mouse, enabling high-resolution mapping of gene regulatory landscape. In particular, analysis of histone modification dynamics in relevant cell types has linked epigenetic abnormalities to disease pathogenesis. This chapter summarizes newly developed protocols tailored to low-input and single-cell profiling, the discovery of novel histone modifications, and epigenetic features of cis-regulatory elements. We will also use examples to demonstrate how histone modification profiles can be utilized to decipher the impact of inherited disease risk variants on regulatory activity and to track tumor evolution. And finally, major areas requiring future investigations are discussed.