Title: Understanding the mechanisms controlling deposition and interplay of co-transcriptional nucleosome modifications
Abstract:
The wrapping of eukaryotic DNA around histones to form nucleosomes allows efficient DNA packaging but is an obstacle for DNA-templated transactions. Multiple regulatory mechanisms have therefore emerged to modulate nucleosomal properties and DNA accessibility. Monoubiquitylation of H2B (H2Bub) on K123 in budding yeast (K120 in humans) is a dynamic co-transcriptional histone modification that modulates chromatin on structural and functional levels. In yeast and higher eukaryotes, the Paf1C transcription elongation factor is required for H2Bub and facilitates its coupling to transcription. A small domain within the Rtf1 subunit of Paf1C, named the Histone Modification Domain (HMD), directly interacts with the multi-functional ubiquitin conjugase Rad6 leading to H2Bub stimulation. Through genetic, biochemical, and genomic approaches, we characterized the highly specific Rad6-HMD interface that allows targeting Rad6 to its nucleosomal substrate. While the molecular events that couple H2Bub to transcription are now coming into focus, the direct contributions of this conserved modification to transcription and its coordination with other epigenetic modifications remain to be fully elucidated. Previous studies revealed a synthetic lethal relationship between H2Bub and H2A.Z, the H2A histone variant that is enriched at the +1 nucleosome of genes. However, it is unclear how these two epigenetic modifications are coordinated and why cells lacking one of the two are so dependent on the other for viability. My ongoing genetic and genomic experiments are directed towards investigating the impact on the transcriptome upon the concurrent loss of H2A.Z and H2Bub and pinpointing mechanisms that are responsible for the synthetic lethality.
Arndt Lab
Friday, December 15th, 2023
12:00PM
Langley A219B