Investigation of the Germline Functions of CFP-1 and MRG-1 in Caenorhabditis elegans Open Access

Krinichanskiy, Daniel (Spring 2022)

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MRG-1 is the C. elegans ortholog of human MRG-15 protein – a factor which recognizes H3K36me3 to guide both histone acetylase and deacetylase complexes to their respective sites in the genome. Though it is known to be an essential epigenetic factor in embryonic and germline development in C. elegans, it was recently shown that its chromodomain (the domain with which it recognizes the histone modification) is not required for normal germline development. These findings suggested that its function within the germline could be redundant with another factor. CFP-1 is another highly conserved protein, likewise shown to be involved in guiding histone deacetylase complexes, and is required for normal establishment and maintenance of H3K4me3. Here, we examine the genetic interactions between the two proteins. Our findings demonstrate that the double knockdown of both CFP-1 and MRG-1 causes synergistic sterility, whereas loss of either alone has no such effect in the generation assayed. They exhibit a novel sterility phenotype, wherein germ cells initially proceed through normal development but are seemingly degraded in older adults. The singular effect of cfp-1 is decreased fertility in both wildtype animals and mrg-1 deletion heterozygotes, whereas the embryonic mortality rate is not affected. Removal of mrg-1 and knockdown of cfp-1 correlates with increases in germline levels of H3K9ac and H3K9me3, which may contribute to the observed phenotype. 

Table of Contents

Index of Figures...7

Chapter 1: Introduction...8

Chapter 2: Results...12

Chapter 3: Discussion...20

Chapter 4: Experimental Design and Methods...24


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