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Research Description:
We are interested in understanding the mechanisms underlying alterations in chromatin structure and how this dynamic process affects the access of enzymatic machinery to its genomic DNA substrate. ATP-dependent chromatin remodeling complexes, like the yeast RSC complex, alter the structure of nucleosomes, the basic repeating unit of chromatin, allowing protein factors to bind to the otherwise relatively inaccessible nucleosomal DNA. Remodelers couple the energy of ATP hydrolysis to translocate along the DNA, resulting in the selective and sequential disruption of one or more of the 14 histone DNA contacts that normally serve to co-ordinately stabilize the nucleosome, thereby resulting in the localized disruption of the DNA along the octamer surface. We would like to understand the mechanistic details of how these alterations occur and how they affect chromatin structure, which in turn, affect whether the chromatin is in an active or inactive state.
The amino-terminal histone tails are heavily modified post-translationally by acetylation, methylation, phosphorylation, and ubiquitination; and these modifications correlate with the regulation of downstream biological process such as transcription, gene silencing, DNA replication and repair. We would like to know how these histone tail modifications affect the action of the chromatin remodeling machines on nucleosomal structure and function.
Research Keywords:
chromatin regulation, nucleosome, histone modification, ATP-dependent remodeling