Defining the Relative Contribution of K27 Methylation and S31 Phosphorylation to Gliomagenesis in DIPG
Abstract
In the first year of this project, we achieved significant progress in deciphering the complex epigenetic landscape governing Diffuse Intrinsic Pontine Gliomas (DIPG). The primary aim was to understand the relative contributions of K27 methylation and S31 phosphorylation to gliomagenesis in H3.3 K27M mutant DIPG. We focused on the role of histone modifications, specifically mutations in histone H3.3, to discern their impact on cellular functions like chromosome segregation and gene expression. Utilizing CRISPR-Cas9 technology, we successfully generated and characterized knockout variants for EZH2 and EZH1, histone methyltransferases responsible for H3K27 methylation. The cells also harbor mutations in H3.3 at K27 and S31 sites, laying the groundwork for multifaceted functional analyses. Preliminary data strongly validate our hypothesis that chromosome missegregation and epigenetic dysregulation contribute to tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1217445
Entities
People
- Edward Hinchcliffe
- James P. Robinson
Organizations
- University of Minnesota