University of Pittsburgh Department of Biological Sciences Presents:
Friday Noon Seminar Series 2017-2018
Graduate Student: Elizabeth Hildreth
The DNA entry-exit site of the nucleosome regulates transcription through maintenance of chromatin structure
Transcription is controlled by factors that remove or modify nucleosomes, allowing Pol II and transcription factors to contact otherwise occluded DNA. The mechanisms by which chromatin is modified are well understood in regard to transcription initiation and elongation. Despite a few studies showing that transcription-coupled histone modifications and select chromatin remodelers are important for proper termination at some candidate loci, little else is known about the role of chromatin at this final termination step. We are further investigating this using Saccharomyces cerevisiae as a model. We have identified residues in H3, H4, and H2A which, when mutated, cause defects in termination. Interestingly, many of these residues reside in or near the DNA entry-exit site of the nucleosome. This protein surface, including portions of histones H3 and H2A, is responsible for regulating the stability of the protein-DNA complex. Genome-wide analysis of our termination-defective histone mutants does indeed reveal altered nucleosome occupancy. RNA sequencing data from two of the H3 mutants reveals up- and down-regulation of many mRNA loci and terminator read-through of most Pol II transcribed snoRNAs, likely explained by the altered nucleosome occupancy observed. In line with previous evidence that increased elongation rate is coupled to transcription read-through, we have also begun assessing Pol II elongation rate in our histone mutants. Together, data so far implicate the DNA entry-exit site as an important player in maintenance of chromatin organization that supports proper regulation of transcription.
Friday, February 2, 2018
A219B Langley Hall
12:00 PM Seminar