The histone variant macroH2A1 (mH2A1) is associated with gene repression but the molecular mechanisms by which it exerts its function are largely unknown. mH2A is recruited to the IL-8 promoter by ATF-2 where it functions as a transcriptional repressor. Interestingly, macroH2A1 has been shown to bind O-acetyl-ADP-ribose (OAADPR).
The functional consequences of this interaction are unknown. This proposal will take two distinct approaches to elucidate the function of mH2A1 in the cell. First, this study will address the detailed mechanism by which mH2A regulates the IL-8 promoter. Specifically, the role OAADPR plays in regulating IL8 transcription will be investigated.
In a second approach, this study will investigate the function of mH2A1 on a genomic level. In a series of micorarray experiments, the functional role of mH2A1 across the genome will be elucidated. Special attention will be given to the role of OAADPR binding and mH2A1 function in this genome-wide analysis.
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