Defining the Consequence of CHD1 Loss on Transcriptional Regulation and Therapeutic Response
Abstract
Genome wide studies have identified a high prevalence of inactivating genomic alterations associated with nucleosome remodeling and modifying enzymes, suggesting that deregulation of chromatin architecture is critical in tumor initiation/progression. CHD1 is a founding member of the chromatin remodeling family, characterized by tandem Chromo-domains, a DNA Helicase domain, and DNA binding domain (CHD1). A multitude of studies have demonstrated that CHD1 is recruited to the promoters of highly transcribed genes by the epigenetic mark H3K4me3, where it redistributes local nucleosomes ahead of RNA polymerase to facilitate efficient transcriptional initiation and RNA processing. While a majority of cell types appear to be dependent upon the function of CHD1, a subclass of primary PC a is characterized by the genomic loss of this chromatin remodeler. Given that PC a is a disease driven by aberrant transcriptional regulation mediated by oncogenic transcriptional factors (e.g. AR and MYC), it is imperative to understand the molecular underpinnings of CHD1 loss in driving these oncogenic programs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2018
- Accession Number
- AD1060303
Entities
People
- Michael A. Augello
Organizations
- Weill Cornell Medicine