Histone Methylation and Epigenetic Silencing in Breast Cancer

Abstract

The purpose of this research is to investigate the role of a chromatin-modifying enzyme called EZH2 in breast cancer epigenetics and to develop strategies to identify chemical inhibitors of this, enzyme. EZH2 is a histone methyltransferase which modifies lysine-27 of histone H3 an epigenetic mark which is generally linked to gene silencing and is implicated in tumor suppressor silencing during breast cancer progression. Progress on this project includes: 1) Identification of target genes that are directly silenced by EZH2 in breast cancer cells and 2) Mapping of EZH2 binding sites within the chromatin of one such target gene. This mapping defines subregions of regulatory DNA likely to contain response elements that mediate EZH2 silencing. The delimitation and characterization of an EZH2 response element is required in the plan for engineering a breast cancer cell-based bioassay to screen for EZH2 inhibitors. These inhibitors provide important drug compounds to test as part of emerging epigenetic therapies to combat cancer.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2008
Accession Number
ADA491094

Entities

People

  • Carol A Lange
  • Jeffrey A. Simon

Organizations

  • University of Minnesota

Tags

DTIC Thesaurus Topics

  • Antineoplastic Agents
  • Biology
  • Breast Cancer
  • Cancer
  • Carcinoma
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Chromosome Structures
  • Colon Cancer
  • Enzyme Inhibitors
  • Genetics
  • Identification
  • Multiprotein Complexes
  • Neoplasms
  • Prostate Cancer
  • Stem Cells

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biochemistry
  • Molecular and genetic basis of cancer.