Identification of novel binding targets of the SWI/SNF complex member SNF5 in malignant rhabdoid tumors Public Deposited

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  • March 20, 2019
Creator
  • Davies, Brian Robert
    • Affiliation: School of Medicine, Curriculum in Toxicology
Abstract
  • Malignant Rhabdoid Tumors (MRTs) show a loss of SNF5, a core subunit of the SWI/SNF chromatin remodeling complex. These cancers are genetically stable, but epigenetically unstable. We hypothesize that SNF5 loss fuels MRT development through aberrant gene expression by disruption of SWI/SNF remodeling. Introduction of SNF5 into MRTs activates the Rb-E2F pathway, resulting in G1 arrest. However, this pathway cannot completely account for the arrest. We identified two novel SNF5 targets that may contribute to arrest by PCR Array, Cyclin G2 and HERC5. Both show an increase in mRNA expression and SNF5 binding to their promoters by ChIP. Use of 4x44k expression arrays revealed that GDF15 might be a third novel target. Expression increases by mRNA and protein, but ChIP is needed for validation. These genes may be regulated by SNF5 and contribute to arrest after chromatin remodeling increases expression, possibly providing further insight into MRT development.
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  • In Copyright
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  • "... in partial fulfillment of the requirements for the degree of Master of Science in the Curriculum in Toxicology."
Advisor
  • Weissman, Bernard
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  • Chapel Hill, NC
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  • Open access
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