Regulation of histone modification and cryptic transcription by the Bur1 and Paf1 complexes

The Bur1-Bur2 and Paf1 complexes function during transcription elongation and affect histone modifications. Here we describe new roles for Bur1-Bur2 and the Paf1 complex. We find that histone H3 K36 tri-methylation requires specific components of the Paf1 complex and that K36 trimethylation is more strongly affected at the 5 ' ends of genes in paf1 Delta and bur2 Delta strains in parallel with increased acetylation of histones H3 and H4. Interestingly, the 5 ' increase in histone acetylation is independent of K36 methylation, and therefore is mechanistically distinct from the methylation-driven deacetylation that occurs at the 3 ' ends of genes. Finally, Bur1-Bur2 and the Paf1 complex have a second methylation-independent function, since bur2D set2 Delta and paf1 Delta set2 Delta double mutants display enhanced histone acetylation at the 3 ' ends of genes and increased cryptic transcription initiation. These findings identify new functions for the Paf1 and Bur1-Bur2 complexes, provide evidence that histone modifications at the 5 ' and 3 ' ends of coding regions are regulated by distinct mechanisms, and reveal that the Bur1-Bur2 and Paf1 complexes repress cryptic transcription through a Set2- independent pathway.