Spt6 Regulates Intragenic and Antisense Transcription, Nucleosome Positioning, and Histone Modifications Genome-Wide in Fission Yeast

Abstract

Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. To gain a comprehensive understanding of the roles of Spt6, we performed genome-wide analyses of transcription, chromatin structure, and histone modifications in a Schizosaccharomyces pombe spt6 mutant. Our results demonstrate dramatic changes to transcription and chromatin structure in the mutant, including elevated antisense transcripts at >70% of all genes and general loss of the +1 nucleosome. Furthermore, Spt6 is required for marks associated with active transcription, including trimethylation of histone H3 on lysine 4, previously observed in humans but not Saccharomyces cerevisiae, and lysine 36. Taken together, our results indicate that Spt6 is critical for the accuracy of transcription and the integrity of chromatin, likely via its direct interactions with RNA polymerase II and histones.

ACKNOWLEDGMENTS

We thank Koon Ho Wong for his help and advice with the ChIP-seq experiments, Dom Helmlinger and Dan Spatt for helpful scientific discussions, and Dan S. Day for helpful comments on the manuscript.

This study was supported by a Wellcome Trust Senior Investigator Award (grant 095598/Z/11/Z) to J.B. and National Institutes of Health grant GM32967 to F.W.