Role of the ubiquitin system in epigenetic regulation

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Ubiquitin, a 76 amino acid small protein, is well conserved from yeast to humans. It can be covalently added onto thousands of different proteins through a process known as ubiquitination to provide diversity and dynamics to cell regulation. Histones are a group of basic nuclear proteins that bind and organize the linear DNA into the structural units called nucleosomes, which are further condensed into chromatin. Ubiquitin modification of histones is directly involved in many vital cellular functions including transcription, DNA replication, repair and gene silencing and therefore plays a critical role in the regulation of cell division, growth and differentiation. The mechanism of this histone modification and the players involved in this process are poorly characterized. The goal of our research program is to understand the mechanism and the importance of ubiquitin modification of histones in cellular regulation.