Linker histone H1 and variant histone H2A.z interactions in gene silencing and chromosome segregation

Wesleyan University received a $598,500 Project Grant award from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective September 1, 2025, through August 31, 2028. The award supports fundamental basic research investigating the interactions between linker histone H1 and variant histone H2A.Z in regulating transcriptional silencing and chromosome segregation in budding yeast. The research will advance understanding of chromatin structure and function through a series of chromatin immunoprecipitation experiments designed to determine the binding interdependence of H1 and H2A.Z across the genome, examine H1's association with silencing factors, and evaluate whether increases in chromosome ploidy in H2A.Z-deficient strains result from H1 influence on kinetochore structure or function.

The project deliverables will include scientific findings on the fundamental mechanisms of histone interactions and their roles in gene regulation and chromosomal stability. These research outcomes are expected to contribute to broader understanding of eukaryotic chromosome biology and may establish foundational knowledge for advances in related biomedical research areas. As a meritorious investigator-initiated research project funded through NIGMS's core mission to support basic research that increases understanding of biological processes, this award exemplifies the Institute's commitment to supporting high-impact scientific research that advances human health and disease understanding.

Abstract

Linker histone H1 and variant histone H2A.z interact to regulate transcriptional silencing and chromosome segregation in budding yeast H1 and H2A.z are highly conserved building blocks of eukaryotic chromosomes that promote e=icient patterns of gene expression and transmission of chromosomes. Our published and preliminary data indicate that a balance of H1 and H2A.z function is required for diverse chromatin-mediated processes in the cell, including heterochromatin- dependent transcriptional silencing and kinetochore function. In particular, our results suggest that H2A.z protects the cell from a potentially deleterious action of linker histone H1. To uncover fundamental aspects of chromatin structure and determine specific functions of histone H1 and H2A.z we will conduct a series of experiments to determine the nature of this relationship. We will conduct chromatin immunoprecipitation experiments to determine the interdependence of H1 and H2A.z's binding through the genome, including across heterochromatic regions and centromere-associated sequences. We will examine histone H1's possible association with silencing factors, and determine if increases in chromosome ploidy observed in strains lacking H2A.z are due to an H1 influence on kinetochore structure or function.