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    Conserved Nucleosome Remodeling/Histone Deacetylase Complex and Germ/Soma Distinction in <em>C. elegans</em>: A Dissertation

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    Authors
    Unhavaithaya, Yingdee
    Faculty Advisor
    Craig C. Mello
    Academic Program
    Cell Biology
    UMass Chan Affiliations
    RNA Therapeutics Institute
    Document Type
    Doctoral Dissertation
    Publication Date
    2003-08-22
    Keywords
    Caenorhabditis elegans Proteins
    Cell Differentiation
    Germ Cells
    Histone Deacetylases
    Nuclear Proteins
    Transcription Factors
    Amino Acids, Peptides, and Proteins
    Animal Experimentation and Research
    Cells
    
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    Abstract
    A rapid cascade of regulatory events defines the differentiated fates of embryonic cells, however, once established, these differentiated fates and the underlying transcriptional programs can be remarkably stable. Here, we describe two proteins, MEP-1, a novel protein, and LET-418/Mi-2, both of which are required for the maintenance of somatic differentiation in C. elegans. MEP-1 was identified as an interactor of PIE-1, a germ-specific protein required for germ cell specification, while LET-418 is a protein homologous to Mi-2, a core component of the nuc1eosome remodeling/histone deacetylase (NuRD) complex. In animals lacking MEP-1 and LET-418, germline-specific genes become derepressed in somatic cells, and Polycomb group (PcG) and SET domain-related proteins promote this ectopic expression. We demonstrate that PIE-1 forms a complex with MEP-1, LET-418, and HDA-1. Furthermore, we show that the overexpression of PIE-1 can mimic the mep-1/let-418 phenotype, and that PIE-1 can inhibit the Histone deacetylase activity of the HDA-1 complex in COS cells. Our findings support a model in which PIE-1 transiently inhibits MEP-1 and associated factors to maintain the pluripotency of germ cells, while at later times MEP-1 and LET-418 remodel chromatin to establish new stage- or cell-type-specific differentiation potential.
    DOI
    10.13028/yr86-6282
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/31546
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    ae974a485f413a2113503eed53cd6c53
    10.13028/yr86-6282
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