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

/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. Project Number: 1R15GM160956-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: SCOTT HOLMES | Institution: WESLEYAN UNIVERSITY, MIDDLETOWN, CT | Award Amount: $598,500 | Activity Code: R15 | Study Section: Special Emphasis Panel[ZRG1 CDB-N (81)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11221444