Mechanisms that couple histone modifications to transcription elongation and regulate transcription termination (108.2)

Abstract

During transcription elongation, multiple regulatory factors associate with RNA polymerase II and coordinate RNA processing and chromatin modification with transcript synthesis. The eukaryotic Paf1 complex (Paf1C) functions at the intersection of RNA synthesis and chromatin modification by traveling with RNA pol II at all active genes, facilitating conserved histone modifications, and stimulating the recruitment of factors important for RNA 3’‐end formation. Using budding yeast as a model system, we are employing a multidisciplinary approach of genetics, biochemistry, structural biology and genomics to dissect these functions of Paf1C. With respect to histone modifications, we are investigating how a 66 amino acid domain within the Rtf1 subunit of Paf1C can substitute for the entire complex in promoting histone modifications in vivo. We are also using a genetic approach to identify amino acids within the nucleosome itself that are important for Paf1C‐dependent histone modifications. In related work, we have shown a role for Paf1C‐dependent histone modifications in regulating RNA 3’‐end formation through the Nrd1‐Nab3‐Sen1 pathway. We are further exploring the functional importance of Paf1C in noncoding RNA synthesis through the use of specific yeast mutant strains and high‐resolution transcriptome analysis.