Federal Project Grant Summary

The University of California, Santa Cruz received a $425,033 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective July 1, 2026 through April 30, 2031. This award funds fundamental research to systematically characterize histone variant protein interaction networks and elucidate the molecular mechanisms governing these interactions. The research employs advanced proteomics and high-resolution structural biology techniques to map nucleosome interactomes, focusing specifically on histone variants H2A.Z, H3.3, and CENP-A (centromeric protein A), which are essential for maintaining genomic integrity and cellular identity.

Over the five-year funding period, the research will determine how different combinations of these histone variants within nucleosomes generate distinct regulatory signals and recruit specific protein complexes to control nuclear functions. A major component involves investigating CENP-A turnover mechanisms, particularly how CENP-A overexpression is controlled through targeted proteasomal degradation during mitosis. The project will utilize cryogenic electron microscopy to visualize at near-atomic resolution how CENP-A is recognized and ubiquitinated by the DCAF11-E3 ubiquitin ligase complex. This work will provide mechanistic insights into variant histone regulation and inform understanding of dysregulation mechanisms implicated in cancer, neurological disorders, and developmental diseases.