Murray White:
Title: TBA
Abstract: TBA
Hatfull Lab
Aakash Grover:
Title: Investigating the direct roles of a histone modification in regulating transcription
Abstract:
The Polymerase Associated Factor 1 complex (Paf1C) is an evolutionarily conserved five-subunit complex that associates with RNA Polymerase II (Pol II) during transcription elongation. Cells that lack a functional Paf1C exhibit transcriptional defects, including impaired Pol II processivity and increased antisense transcription. Paf1C (particularly subunits Paf1, Ctr9, and Rtf1) is also critical for the deposition of a single ubiquitin on lysine 123 of histone H2B in yeast (K120 in humans). H2BK123 mono-ubiquitylation (H2BK123ub) occurs co-transcriptionally and is essential for the deposition of other histone modifications. Previous work detailing the transcriptional effects of Paf1C utilized cells lacking a functional Paf1C. These cells also lack H2BK123ub and its dependent histone modifications. The degree to which the absence of these modifications contributes to the transcriptional defects observed in Paf1C mutants is unknown. We hypothesize that some of these transcriptional defects are due to the loss of H2BK123ub. To test this, we have developed a ß-estradiol-based induction system to recover H2BK123ub in yeast strains lacking Rtf1 or both Rtf1 and Paf1. We show that H2BK123ub and downstream histone modifications can be recovered in cells lacking Rtf1 as soon as 2 hours after ß-estradiol treatment. Interestingly, the recovery kinetics of these histone modifications in cells lacking both Rtf1 and Paf1 are different. We can now utilize time-resolved genomic approaches to test whether we can suppress any transcriptional defects by re-introducing H2BK123ub in Paf1C-deficient cells. This study will provide insights into how a transcriptionally-associated histone modification contributes to transcriptional regulation.
Arndt Lab
Friday, September 22nd, 2023
12:00PM
Langley A219B