Show simple item record

dc.contributor.advisorCraig C. Mello
dc.contributor.authorUnhavaithaya, Yingdee
dc.date2022-08-11T08:08:40.000
dc.date.accessioned2022-08-23T16:03:47Z
dc.date.available2022-08-23T16:03:47Z
dc.date.issued2003-08-22
dc.date.submitted2007-01-23
dc.identifier.doi10.13028/yr86-6282
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31546
dc.description<p>Some images did not scan well. Please consult original document.</p>
dc.description.abstractA 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.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectCaenorhabditis elegans Proteins
dc.subjectCell Differentiation
dc.subjectGerm Cells
dc.subjectHistone Deacetylases
dc.subjectNuclear Proteins
dc.subjectTranscription Factors
dc.titleConserved Nucleosome Remodeling/Histone Deacetylase Complex and Germ/Soma Distinction in C. elegans: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1239&amp;context=gsbs_diss&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/239
dc.legacy.embargo2017-04-24T00:00:00-07:00
dc.identifier.contextkey244400
refterms.dateFOA2022-08-24T04:06:18Z
html.description.abstract<p>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 <em>C. elegans</em>. 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 <em>mep-1/let-418</em> 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.</p>
dc.identifier.submissionpathgsbs_diss/239
dc.contributor.departmentRNA Therapeutics Institute
dc.description.thesisprogramCell Biology


Files in this item

Thumbnail
Name:
Unhavaithaya_Yingdee.pdf
Size:
5.254Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record