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A genome-wide RNAi screen for genes that interact with the C. elegans PcG genes sop-2 and sor-3 Export

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c04e72 c08c31 c09g45 c50e104 caenorhabditis_elegans celegans c_elegans egl-5 elegans meeting_abstract mes-6 nematode sop-2 sor-1 sor-3 wormbase zk12363

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" Polycomb group (PcG) proteins play an important role in specifying the positional identities of cells by transcriptionally regulating the expression of Hox genes. PcG proteins also function in other processes such as in tumorigenesis and in the self-renewal of stem cells. However, the study of molecular mechanisms of PcG-mediated gene repression in fly and mammals is hindered by the complexity and redundancy of the PcG complexes. We previously showed that C. elegans contains relatively simple PcG complexes (1,2). sop-2 encodes a novel protein that is functionally and structurally related to PH and SCM of the PRC1 PcG complex. sor-3 encodes a novel protein containing an MBT domain, suggesting that it may constitute the PhoRC-like PcG complex in C. elegans. We also demonstrated that mutations in sop-2 cause synthetic lethal in combination of a mutation in sor-1 (encoding a component of the PRC1 complex), sor-3 or mes-6 (encoding a component of the ESC/E(Z) complex). Furthermore, the expression domains of the Hox gene egl-5 were dramatically expanded in the double mutants. The genetic interactions suggest that the distinct PcG complex could function together in gene regulation or, alternatively, that they act in parralle pathways. To further understand the underlying mechanisms of PcG-mediated gene repression, we performed a genome-wide RNAi screen to identify mutants that are synthetic lethal with sop-2 or sor-3 mutants. 70 RNAi clones were identified from 16,540 RNAi clones screened (targeting about 86% of the genome). We found that a large number of identified genes were previously implicated in chromatin remodeling or in regulating the germline tumor formation. We are further characterizing these putative PcG enhancers. Our study shows that PcG genes interact with multiple chromatin remodeling complexes in regulating the expression of Hox genes. Furthermore, PcG genes function in many biological processes, including vulva formation, specification of dopaminergic and serotonergic neurons and germline tumor formation.1. Zhang et al., Dev. Cell 20032. Zhang et al., Development 2006"


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