In the eukaryotic nucleus, chromatin is constantly reshaped to allow proper gene expression during development and homeostasis. The nucleosome, the repeat unit of chromatin, is also dynamic. A variety of regulatory cofactors, including chromatin remodeling factors, histone chaperones, post-translational modification writers and general transcription factors, actively change the position and composition of nucleosomes. The activities of these factors may result in the formation of different types of subnucleosomal species. Subnucleosomal species are often found in gene regulatory regions, such as promoters and enhancers, and their presence correlates well with the gene activity. The formation of subnucleosomal particles likely increases the accessibility of the underlying DNA to the transcription machinery. Understanding these subnucleosomal species is therefore essential for uncovering the mechanisms of gene expression. This knowledge will have a broad impact on a diverse range of biological research, including development and cancer biology.
My long-term research goal is to expand our mechanistic understanding of subnucleosomal chromatin particles by investigating the formation and functions of these key components of active chromatin. For the next several years, my group will tackle these fundamental problems from multiple angles, which would range from the use of purified and defined biochemical systems to cell-based, next generation sequencing (NGS), bioinformatics and other genome-wide techniques.