Structural and Functional Studies of Chromatin

Project Summary Chromatin dynamics play a critical role in many cellular processes, including gene expression, DNA replication, DNA repair, cell division and differentiation. These processes require changes to chromatin structure, which are regulated by a variety of molecular mechanisms, such as histone modifications, ATP-dependent chromatin remodeling or transcription factors activity. My laboratory studies the dynamics of active and silent chromatin states, using structural biology, biochemistry, molecular biology and genetics. My lab’s research has currently two primary themes, stemming from our previous functional and structural work on chromatin. The first theme focuses on the biology of repetitive elements. We combine genetics, genomics and molecular biology to understand how genomes can differentiate their own (self) DNA from foreign (non-self) DNA such as transposable elements. In this theme we also study the role of rDNA chromatin in ribosome biogenesis. The second theme focuses on the mechanisms of chromatin dynamics and modifications. We combine structural biology with biochemistry and molecular biology to understand how chromatin dynamics and histone modifications modulate cooperative binding of transcription factors and how the latter cooperate with ATP-dependent chromatin remodelers to increase accessibility of DNA their binding sites. Another interest of the laboratory is the dynamics of DNA movements on nucleosome by chromatin remodelers. We are uniquely positioned to probe those fundamental questions by combining various approaches, ranging from structural biology to cell biology and genomics, and we will continue to push the boundaries of cryo-EM beyond static structures. Our long-term goal is to understand the regulation of genome expression by chromatin and how mutations in chromatin proteins contribute to oncogenesis, which may provide new ways of cancer treatment.