Identification of histone crotonylation specific chromatin remodeling mechanisms in intestinal cells

Abstract

The human colon provides an ecosystem for a huge number and diversity of microbes, mostly bacteria. These are normally commensal or beneficial, as they play an important role in the digestion of food matter and contribute to the generation of bioactive molecules, such as vitamins and short chain fatty acids. They also have important functions in the defense against pathogens and immunity. The interaction between these microbes and the host is tightly regulated, to nurture beneficial interactions, while preventing pathogenic invasion or aberrant inflammatory responses. Especially the last few years have revealed the broad, systemic importance of the gut microbiota-host interactions for our understanding of health and disease. We will illuminate mechanisms of gut microbiota-host interaction by focusing on gene regulatory pathways involving chromatin dynamics, using mouse models. In particular, we will focus on the microbiota dependent histone posttranslational lysine modification crotonylation and how this is involved in gene regulation in the intestinal epithelium. We will study factors that specifically interact with crotonylated histones and we will reveal the function of all these components in the microbiota-host crosstalk. This research will uncover new pathways and new drug targets with potential relevance to Colitis and Cancer. (AU)