RUI: Defining histone variant regulatory mechanisms for sperm-specific gene expression

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Fertility depends on properly formed sperm, oocytes, and embryos. A critical factor to form each unique cell type is the regulation of distinct sets of genes during development. However, how cells coordinate the expression of sets of genes that control cell fate before and after fertilization is still mysterious. In this project, the investigator's studies use C. elegans, a model worm organism, to focus on key regulators of gene expression called histone H2A variants. The goal of this project is to define the specialized mechanisms used by a specific H2A variant to regulate distinct sets of genes required for sperm and embryo development. This work will be conducted at San Francisco State University, an urban minority-serving public institution with a mostly undergraduate student population. The investigators will engage the diverse students directly in the research to apply molecular, computational, and cytological methods to determine H2A variant gene regulation mechanisms. Students will publish their research in traditional journals or "micropublication: biology", a new platform to provide rapid peer-reviewed, high-quality findings directly to the public. These studies will advance the career development of diverse students in STEM fields. The investigators will determine roles of the C. elegans sperm-specific histone H2A variant HTAS-1 in three aims. In Aim 1, students will use RNA-seq to define how HTAS-1 regulates transcription of target sites during sperm formation. In Aim 2, students will mine data from public databases and collaborators to define overlap of HTAS-1 with histone modifications, transcription factors, tissue-specific transcripts, and cis elements that specify sperm fate or regulate gene expression. Differences in transcriptomic profiles in the absence of HTAS-1 will support HTAS-1 function in mechanisms of transcriptional initiation, elongation, and co-transcriptional processing linked to H2A variants in other systems. In Aim 3, they will follow the dynamics of HTAS-1-dependent expression of individual genes before and after fertilization to determine epigenetic roles of HTAS-1. Together, these approaches will define co-regulators, cis regulatory elements, and mechanisms that H2A variants use to regulate gene expression during sperm differentiation and embryo development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.