Research in my laboratory is focused on understanding how chromatin remodeling complexes regulate chromatin structure and gene expression in the budding yeast, Saccharomyces Cerevisiae.
Modulation of chromatin structure plays a central role in all the activities of the Eukaryotic genome (e.g. gene expression, DNA replication, DNA repair, mitosis and meiosis). The Chromatin structures can influence the binding and function of the numerous proteins that collaborate in all these different events involving the genome.
We are mainly interested in the role played by two protein complexes that remodel the chromatin structure and regulate gene expression with an emphasis on cell-cycle dependent transcription: (i) the SWI/SNF complex, an ATP-dependent chromatin remodeling complex, which was the first chromatin remodeling complex to be identified (ii) the HIR co-repressor complex that I recently characterized as a novel nucleosome assembly factor.
The role of chromatin remodeling complexes, such as the SWI/SNF complex, is known to be broadly required for transcriptional regulation, but their specific roles in cell cycle-dependent transcription remain largely unknown. The recently characterized HIR co-repressor complex, which constitutes a novel nucleosome assembly factor, plays also an important role in the regulation of gene transcription and particularly on the cell cycle-dependent histone genes. I also identified a very unique feature of the HIR complex which can block SWI/SNF chromatin remodeling activity in vitro, highlighting a potential important role for gene regulation in vivo.
The goal of my laboratory is to gain a detail understanding of the mechanisms played by the yeast SWI/SNF chromatin remodeling complex and the HIR co-repressor complex in gene expression and particularly in cell-cycle dependent transcriptional regulation. This will give us considerable insight on how the chromatin structure is regulated in a cell cycle dependent manner.
Furthermore, this work has wider implications in that the chromatin remodeling factors studied, SWI/SNF and HIR (human homologue HIRA), are important in the control of genes involved in development as shown by the embryonic lethality of the corresponding knock-out in mice. They are likely to play important role during stem cells differentiation and epigenetic regulation. Their implication in carcinogenesis is well-documented and SWI/SNF complex is commonly referred as a tumor suppressor "complex".
Therefore, these studies are helping us to understand how perturbations in these processes affect gene transcription, cell cycle progression, and genetic instability which are important steps leading to human diseases including cancer, leukemia and lymphoma.