UC Merced

Nucleosomes in eukaryotes achieve the tradeoff between compact packaging for genome stability and inheritance, and accessibility for gene expression, by deploying histone variants with specialized chromatin functions. While some histone variants are highly conserved across eukaryotes, others have evolved to play crucial roles and carry out lineage-specific functions. The origins and functional roles of many histone variants remain largely unknown, and investigations into the evolution and functional roles of histone variants can provide a foundation for understanding the participation of chromatin in epigenetic memory and in critical cellular processes. This doctoral study furthers the understanding of the regulatory roles and evolutionary history of the mysterious histone H2A variants of C. elegans, namely, the ancient H2A.ZHTZ-1, sperm-specific HTAS-1, and HIS-35. This study describes the mechanism of the incorporation and dynamics of the H2A variants, HTAS-1 and HTZ-1, during spermatogenesis. It elucidates that the variant HTZ-1 is expressed throughout the male germline, whereas HTAS-1 is expressed in the proximal germline during later stages of sperm formation. HTZ-1 regulates transcription around the promoters during sperm formation, thus turning the gene On/OFF, whereas HTAS-1 may replace HTZ-1 during transcription and can provide sperm-specific re-packaging. Therefore, HTAS-1 may act for temporal gene regulation, as a replacement histone, for specific packaging of paternal info. The findings of the study suggest that in hermaphrodites, HTZ-1 activates germline genes during oocyte formation, whereas it represses sperm-specific genes during oocyte formation. This investigation also restructures the story of ‘how’ and ‘when’ the three H2A variants of C. elegans got evolved from their canonical counterparts. It is depicted that HTZ-1 is an ancestral histone which appeared long before the nematodes. HTAS-1, on the other hand, evolved fairly recently, and it was incorporated in the ancestor of Caenorhabditis, whereas HIS-35 evolved somewhere in the ancestor of Caenorhabditis and Diploscapter.