Radzisheuskaya Lab
Research Overview
In the eukaryotic nucleus, the DNA is packaged hierarchically as chromatin. The nucleosome is the first level of this hierarchy, composed of an octamer of four histone proteins and a DNA segment wrapped around it. At higher organizational levels, nucleosomes are assembled into fibers, loops, domains, and compartments, forming a dynamic structure that regulates all DNA-dependent processes and protects genome integrity.
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The significance of chromatin regulation in controlling cell phenotype is highlighted by altered epigenomes and frequent mutations in genes that encode chromatin-modifying enzymes in a range of diseases, from neurological disorders to cancer. Since epigenetic changes are potentially reversible, targeting chromatin therapeutically represents an attractive approach. However, identifying promising drug targets and selecting patients who would benefit from them requires a thorough understanding of the underlying molecular mechanisms, which is the main interest of our research group.
The side chains of histone proteins undergo numerous post-translational modifications, which play an important role in regulating chromatin function. Generally, acetylation of lysines on histones is believed to decompact chromatin and thus provide local DNA access for genomic processes. Many histone acetyltransferases are essential for normal development, and some serve as oncogenes or tumor suppressors, further emphasizing the significant roles of histone acetylation in controlling cell state.
Our laboratory focuses on the role of histone acetylation in regulating gene expression and maintaining genome stability during normal development. We also investigate how its misregulation contributes to the development of cancer, specifically acute myeloid leukemia. To address these questions, we develop cutting-edge cellular and mouse genetic models and use a combination of genomics, proteomics, cell biology, and biochemistry approaches.