Abstract 1245 Chromatin mechanisms and genome maintenance functions of histone code writers

Histone post-translational modifications (PTMs) play a central role in genome function. Studies show that a vast number of covalent modifications, such as acetylation, methylation, ubiquitylation and phosphorylation exist on histones. These studies also indicate that histone PTMs work together in the form of a 'histone code' that functions, in part, through the direct recruitment of effector proteins utilizing specialized "reader" domains. While many principles of histone function have been elucidated, our understanding of how histone PTMs contribute to chromatin structure and function is still incomplete. This gap of knowledge is significant, as large exome sequencing studies have revealed that many histone-modifiers, chromatin remodelers, and histone chaperones are dysregulated in a wide range of human diseases, most notably cancer. Our lab is therefore focused on understanding how the chromatin-modifying machinery and histone PTMs contribute to chromatin biology, and in particular, gene regulation. In this lecture, I will cover new insights into 1) the crosstalk between histone acetylation and histone methylation and 2) an unexpected role for the SETD2 histone methyltransferase in genome integrity. This work is supported by NIGMS