DISTINCT BIOPHYSICAL PROPERTIES IMPARTED BY H2A VARIANTS ON CHROMATIN COMPACTION
Israel Saucedo Gonzalez1, Ahmad Nabhan1, Francisco Guerrero1, Diana Chu1, Geeta Narlikar2.
1San Francisco State University, San Francisco, CA, 2University of California, San Francisco, San Francisco, CA.
An organism’s ability to regulate gene expression and chromatin compaction is important to maintain proper function, genomic integrity, and development. Organisms accomplish this by incorporating small, basic proteins called histones into their genome, allowing the formation of transcriptionally active and silenced regions. Additionally, histone variants that differ in protein sequence from canonical histones regulate various chromatin processes. For example HTZ-1, an evolutionarily conserved H2A variant, localizes to the promoter region of developmental genes where it may poise genes for expression. Similarly, HTAS-1, a sperm-specific H2A variant, localizes to condensing chromatin during sperm development. How H2A histone variants function in distinct chromatin processes remains elusive. We hypothesize that variations in amino acid sequence at specific domains confer structural differences and are responsible for their function in distinct processes. We show HTZ-1 and HTAS-1 confer stability to the nucleosome when compared to canonical H2A, and that the C-terminal domain of HTZ-1 is responsible for the increased nucleosomal stability. To understand the impact of H2A variants incorporation in chromatin compaction, we are assembling arrays of nucleosomes in vitro. This will reveal the biophysical properties imparted by HTZ-1 and HTAS-1 on the compaction of larger chromatin structures. The results from this study will elucidate how structural features of H2A variants correlate with their function in active and repressive gene expression. This will provide mechanistic insight into the compaction of the genome, a process crucial for proper gene expression and survival of the organism.