Charting histone modifications and the functional organization of mammalian genomes

Abstract

A succession of technological advances over the past decade have enabled researchers to chart maps of histone modifications and related chromatin structures with increasing accuracy, comprehensiveness and throughput. The resulting data sets highlight the interplay between chromatin and genome function, dynamic variations in chromatin structure across cellular conditions, and emerging roles for large-scale domains and higher-ordered chromatin organization. Here we review a selection of recent studies that have probed histone modifications and successive layers of chromatin structure in mammalian genomes, the patterns that have been identified and future directions for research.

Epigenetic regulation mechanisms of microRNA expression

“…While lysine acetylation can relax the chromatin structure and enhance transcription activation, lysine methylation can cause different effects on gene expression, depending on the positions and degree of methylation. Methylation at H3K4, K36 and K79 is associated with gene activation, whereas methylation at H3K9, H3K27 and H4K20 correlates with transcriptional repression (77,78).…”

“…Chromatin is integrated by nucleosomes, which consist of DNA wrapped twice around a histone octamer, each containing two copies of four highly conserved histones (H2A, H2B, H3, H4), which are susceptible to PTMs, including methylation, acetylation, phosphorylation, ubiquitination, biotinylation, sumoylation and ADPribosylation (77,78). In fact, the most well-studied types of modifications are lysine acetylation and methylation.…”

Application of a systems approach to study developmental gene regulation

“…The chromatin is classically categorized into euchromatin, for open accessible chromatin, and heterochromatin, for close inaccessible chromatin. In addition, the chromatin is marked by different histone modifications (Gaspar-Maia et al 2011;Zhou et al 2011). Different domains of chromatin mark changes dynamically during development.…”

Assembling a COMPASS

“…[33][34][35] Finally, recent studies in yeast COMPASS demonstrated that histone H2B monoubiquitination regulates the H3K4 mono-and di-methylation are now commonly known to be enriched in transcriptional enhancer elements at active and potentially active genes, respectively, while trimethylation of the same residue is a mark associated with the transcriptional start sites of actively transcribed genes. 10,11 Additional analysis of the COMPASS complex revealed that several of its protein subunits (Cps) were evolutionary conserved. Cps60 (also referred to as Bre2) shared high sequence homology with drosophila Ash2, a trithorax protein required for the controls of genes important for disc patterning in flies 12 ( Table 1).…”