The histone H3 mutations found recently found in cancers have dramatic downstream effects on the landscape of the epigenome ? chromatin state and DNA methylation ? with eventual secondary outcomes manifested in gene expression and cellular phenotypes. Modern functional genomics approaches provide invaluable tools to study the effects of this epigenome-mediated cascade. In this Core activity, we will establish a set of genomics tools and computation methods to elucidate the mechanisms through which H3 variants impact the epigenome, transcriptome, and finally the cell during neoplastic transformation.
Cancer progression is associated with massive global aberrations of genome and epigenome organization. Modern genomics technologies have provided invaluable new insights into molecular mechanisms of cancers, including the discovery by our team members of the histone mutations that are the subject of this proposal. The establishment of this Core will provide team members with state of the art genomic and computational tools to unravel the mechanisms of action of histone mutations.
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