Lsh, a Guardian of Heterochromatin

Epigenetic modifications comprise histone modifications, histone variants, nucleosome occupancy and DNA methylation  and are crucial for organization of the genome into active chromatin (euchromatin) and repressed chromatin (heterochromatin). The functional organization of chromatin is important for regulation of transcription, cellular differentiation, and genome maintenance. Our group studies the role of epigenetic modifications that control chromatin structure during normal embryonic development and in human disease.

The current focus of our studies is to understand the molecular mechanisms and biological role of LSH (Lymphoid specific helicase) that my group has discovered. LSH or HELLS (Helicase, lymphoid specific) is an ATPase dependent SNF2 family member and is critical for murine development. LSH mutation in human cause the ICF4 syndrome a complex disease with immunodeficiency, centromeric instability and facial anomalies.

Our recent work indicates that LSH induces deposition of macroH2A in the genome and acts a histone variant exchange factor. We are currently addressing the question of how LSH molecular function alters chromatin structure and influences genomic stability and cellular differentiation. These studies should provide insights into a number of basic biologic processes that involve epigenetic modifications such as transcription, DNA repair, replication and recombination.