Jessica Hauth [class:all]
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Tom Ratliff, William Kelly, Jessica Hauth, Valarie Vought, Eleanor Maine, Mitsue Ohmachi, Valerie Reinke
[
International Worm Meeting,
2005] Cellular RNA-directed RNA polymerases (RdRPs) function in development and RNA silencing in many species and in heterochromatin assembly in S. pombe. EGO-1/RdRP is required for fertility and a robust RNAi response in the C. elegans germ line. EGO-1 activity promotes germ cell proliferation, meiotic progression during leptotene/zygotene, and formation of functional gametes. Many cellular processes rely on EGO-1 activity, including heterochromatin assembly and distribution of nuclear pore complexes and P granules. We hypothesize that different aspects of the ego-1(0) null phenotype reflect roles for EGO-1 in distinct cellular processes. We have focused on describing the role of EGO-1 in heterochromatin assembly. EGO-1 activity is required for methylation of histone H3 on lysine 9 (H3meLys9), a modification associated with transcriptional silencing, on unpaired chromosomes and chromosome fragments in the germ line. EGO-1 activity is not required for all H3meLys9 accumulation in the germ line, since normal accumulation is seen on paired chromosomes and highly repetitive DNA in ego-1(0) mutants. The latter result is consistent with our earlier finding that EGO-1 is not required for transcriptional silencing of repetitive transgenes. H3meLys9 accumulates normally on unpaired chromosomes in dcr-1(0) mutants. In other systems, components of the RNAi machinery, including Dicer, function in targeting heterochromatin to repetitive DNA at centromeres. Therefore, EGO-1 activity may target heterochromatin assembly by a mechanism distinct from the classic RNAi-based mechanism that has been described in other systems. Consistent with a role in chromatin regulation, ego-1 interacts genetically with mutations in other chromatin regulators to disrupt germline development. We propose that EGO-1-mediated heterochromatin assembly may function as a defense against expression of transposons during meiosis/gametogenesis and in the regulation of endogenous gene expression. We used gene expression profiling to identify potential targets of regulation by EGO-1, and have identified sets of genes whose transcript levels are either increased to decreased at least two-fold in ego-1(0) mutants. Our data suggest that EGO-1 activity promotes a pattern of gene expression that is appropriate for germline function.
[
European Worm Meeting,
2006] Maaike C. W. van den Berg1,2, Jessica Z. Woerlee2, Hansong Ma1,2 & Robin C. May1. Cryptococcus neoformans is the causative agent of cryptococcosis, a fatal fungal disease of immunocompromised patients. Our group and others have made use of C. elegans as an alternative host for Cryptococcus, in order to investigate the molecular basis of host-pathogen interactions. Using this system, we now report that male C. elegans show greater resistance to killing by Cryptococcus than hermaphrodite animals and that this resistance can be induced in hermaphrodite animals by inappropriate activation of the male sex-determination pathway. Resistance is molecularly determined, rather than resulting from behavioural changes or reproductive differences, and requires the activity of the stress-response transcription factor DAF-16. Finally, we demonstrate that resistance to Cryptococcus neoformans correlates broadly with longevity within the Caenorhabditis genus. Our results suggest that many of the molecular determinants of longevity and immunity are the same and that differential regulation of these determinants may underlie much sex-dependent and species-dependent variation.
