Friday, 13 February 2015

Mapping Cell-Specific Histone Acetylation

Changes to intracellular metabolism can alter the expression of specific histone methyltransferases and acetyltransferases conferring widespread variations in epigenetic modification patterns. Although important enzymes and chromatin changes have been described, defining the specific process governing the cell’s ability to sense environmental change in development and adulthood at the level of gene expression is an important challenge facing the field. 

Reminiscent of early single-loci genetic studies, many epigenomic investigations have examined specific modifications in isolation. Increased availability of public epigenome-wide datasets has greatly enhanced our understanding of the chromatin landscape. For instance, profiling of chromatin modifications in conjunction with gene expression allows the generation of detailed cell-type and stimuli-specific epigenetic maps. 

Our recent review published in Circulation Research (Feb 2015) discusses the most recent key findings that link cellular metabolism with chromatin-dependent gene changes, including histone acetylation. Read the full article here.

This plot of human chromosome 12 shows the variation of histone H3 lysine 9 acetylation (H3K9ac) among cell types. The outer ring represents ≈134 million base pairs showing some of the estimated 1200 protein coding genes represented in blue and red, including long intergenic nonprotein coding RNA (LINC) and short noncoding or micro RNA (MIR). Differential H3K9ac is represented in each concentric ring shown in blue bar charts proportional to the H3K9ac signal or score for each region. The innermost track represents aortic endothelial (primary human aortic endothelial) showing histone acetylation (green) and deacetylation (orange) conferred by pharmacological histone deacetylase (HDAC) inhibition. Histone acetylation data are generated by chromatin immunoprecipitation combined with sequencing (ChIP-seq) derived from ENCODE and accessed from UCSC. Click image to enlarge. 


Keating ST & El-Osta A. Epigenetics and Metabolism. Circulation Research doi: 10.1161/CIRCRESAHA.116.303936