Professor, Biochemistry & Biophysics
Oliver Smithies Investigator
Cancer Cell Biology
Area of Interest
DNA is faithfully packaged within the nuclei of our cells through the actions of histone proteins. These proteins create individual histone-DNA complexes referred to as nucleosomes, which are further folded into higher-order chromatin structures that are still poorly defined. To a large extent, chromatin structure and function is dictated by histone post-translational modifications, which include acetylation, methylation, ubiquitylation and phosphorylation. Studies indicate that these modifications work together in the form of a ‘histone code’ to regulate the recruitment of effector proteins that then alter the structure and function of chromatin.
Although chromatin has been studied intensely, we still know very little regarding how distinct chromosomal domains such as “euchromatin” and “heterochromatin” become established and maintained, and how the underlying DNA within this highly compact and repressive environment is made accessible to the protein machineries that need to utilize it.is addressing these issues by examining the process of RNA polymerase II transcription. We aim to understand how gene transcription occurs at the “right place” and at the “right time” in the genome, and the mechanisms by which histones, histone variants, and histone post-translational modifications contribute to this event. Recently, the Strahl lab and others have identified roles for several histone-modifying enzymes during the transcription process. These enzymes associate with the polymerase during transcript elongation and alter the chromatin environment to make it more or less permissive for transcriptional initiation and elongation events. As an example, co-transcriptional methylation of histone H3 at lysine 36 by Set2 results in the recruitment of a histone deacetylase complex that keeps the coding region of genes in a more repressed state that is resistant to inappropriate transcriptional initiation and histone exchange. Current efforts are aimed at understanding how this and other histone-modifying enzymes contribute to chromatin organization, nucleosome stability and gene regulation.
Strahl’s group is also engaged in a high-throughput proteomics project involving histone peptide arrays to decipher how histone modifications, and the histone codes they generate, regulate the recruitment of chromatin-associated proteins that govern the diverse functions associated with DNA. These exciting projects are helping to bring new insight into how histones, and the modifications they contain, drive fundamentally important biological processes such as gene transcription and DNA repair in cells, and how their mis-regulation leads to human diseases such as cancer.
Awards and Honors
- UNC Excellence in Basic Science Mentoring Award, 2019
- UNC Excellence in Basic Science Mentoring Award, 2018
- Oliver Smithies Investigator, UNC, 2018
- Ruth and Phillip Hettleman Prize for Artistic and Scholarly Achievement, UNC-Chapel Hill, 2009
- Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) award, 2008
- Jefferson-Pilot Fellow in Academic Medicine, UNC-Chapel Hill, 2006
- ASBMB Schering-Plough Research Institute Award for outstanding research contributions to biochemistry and molecular biology, 2005
- Pew Scholar in the Biomedical Sciences, 2004
- Presidential Early Career Award (PECASE), 2003