Histone Methylation and Epigenetic Silencing in Breast Cancer
Abstract
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 linked to gene silencing and implicated in tumor suppressor silencing during breast cancer progression. Progress on this project includes: 1) Identification of target genes directly silenced by EZH2 in breast cancer cells, 2) Mapping of EZH2 association within the chromatin of one such target gene, 3) Demonstration that a DNA-binding protein, called YY1, co-localizes at this target chromatin, and 4) Evidence that YY1 is needed for silencing and EZH2 chromatin binding at this target gene. These results suggest that YY1 binding sites may help define response elements that recruit and mediate EZH2 silencing in breast cancer cells. The definition of EZH2 response elements is required to engineer 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2010
- Accession Number
- ADA542206
Entities
People
- Jeffrey A. Simon
Organizations
- University of Minnesota