Comparative analysis of histone modification marks in human and murine monocyte subpopulations

Coordinator:		Prof. Dr. Norbert Hübner
Institution:		Max-Delbrück-Centrum for Molecular Medicine Berlin-Buch, Experimental Genetics of Cardiovascular Diseases
Homepage:		www.mdc-berlin.de

Chronic inflammation drives atherosclerosis and the accumulation and continued recruitment of leukocytes are associated with the development of vulnerable plaques that may rupture and lead to thrombosis, myocardial infarction, or stroke. Plaque macrophages account for the majority of leukocytes in plaques, and are believed to differentiate from monocytes recruited from circulating blood. However, monocytes represent a heterogeneous circulating population of cells. Improved understanding of the regulation of gene expression of the different monocyte subpopulations will help to understand the selective contributions of specific monocyte cell types to atherogenesis and will provide a better understanding of the pathophysiology of atherosclerosis.

Epigenetic factors play an important role in genome organization, stability and the control of gene expression. Being the mediator between genetic factors and environment, the epigenome has a profound effect on genome activity. Epigenetic changes are unique for each cell type in a multicellular organism and a key component through which a complex organism can change its expression repertoire and form different tissues and organs while all cells hold the same genetic information. Epigenetic mediators include DNA methylation, posttranslational modifications of histones and certain types of non-coding RNA that, in conjunction with chromatin remodelling complexes, define active and repressed regions of the genome.

The main objective of our project was the systematic characterization of two main monocyte subsets (CD14++CD16-) and (CD14+CD16+) regarding gene expression, active (H3K4me3) and repressive (H3K27me3) methylation marks. By genome-wide mRNA sequencing we analyzed alternative splicing in monocyte subpopulations and differential gene expression profiles. Our studies were comparatively conducted in human and mice.