We use the model organism C. elegans to understand how chromosome architecture and dynamics influence gene expression and male fertility.
Epigenetic Paternal Information
Histones are proteins that package DNA. We've identified a histone H2A variant in C. elegans we have named HTAS-1. Our initial analysis has revealed that HTAS-1 is a sperm-specific histone H2A variant. We are using genetic analysis to determine if worms with a mutant htas-1gene are infertile. We've shown that HTAS-1 is indeed required for optimal fertility and are now currently investigating the role of HTAS-1 in chromosome compaction by fluorescence microscopy.
Because histone H2A variants in other organisms are important for gene expression, we are also determining if HTAS-1 is important for regulating gene expression during sperm formation. Initial DNA microarray data has indeed identified many genes whose expression is changed in the htas-1 mutant. We are now investigating the role of HTAS-1 in regulating these genes.
In addition, because HTAS-1 protein differs from canonical H2A proteins in the sequence of the N-terminal tail region (which is known to be post-translationally modified), we are characterizing post-translational modifications that occur on this sperm-specific histone H2A variant.
Partitioning chromosomes during sperm formation
Chromosome segregation during sperm meiosis differs from that of oocyte meiosis and mitosis. We are interesting in defining how these differences are implemented.
We have identified a set of phosphatase proteins we call GSP-3 and GSP-4 that play roles in sperm chromosome segregation. We are characterizing the role of GSP-3 and GSP-4 using genetic mutant analysis and immunostaining. In order to differentiate how the sperm-specific phosphatases (GSP-3 and GSP-4) differ in function from phosphatases found in oocyte meiosis and mitosis (GSP-1 and GSP-2), and characterizing how GSP-1 and GSP-2 function in sperm meiosis. We are also initiating efforts to look for proteins that interact directly with GSP-3 and GSP-4 by coimmunprecipitation.