Spt6 Is Required for the Fidelity of Promoter Selection

Stephen M Doris; James Chuang; Olga Viktorovskaya; Magdalena Murawska; Dan Spatt; L Stirling Churchman; Fred Winston

doi:10.1016/j.molcel.2018.09.005

Spt6 Is Required for the Fidelity of Promoter Selection

Mol Cell. 2018 Nov 15;72(4):687-699.e6. doi: 10.1016/j.molcel.2018.09.005. Epub 2018 Oct 11.

Authors

Stephen M Doris¹, James Chuang², Olga Viktorovskaya¹, Magdalena Murawska¹, Dan Spatt¹, L Stirling Churchman¹, Fred Winston³

Affiliations

¹ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
² Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
³ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].

Abstract

Spt6 is a conserved factor that controls transcription and chromatin structure across the genome. Although Spt6 is viewed as an elongation factor, spt6 mutations in Saccharomyces cerevisiae allow elevated levels of transcripts from within coding regions, suggesting that Spt6 also controls initiation. To address the requirements for Spt6 in transcription and chromatin structure, we have combined four genome-wide approaches. Our results demonstrate that Spt6 represses transcription initiation at thousands of intragenic promoters. We characterize these intragenic promoters and find sequence features conserved with genic promoters. Finally, we show that Spt6 also regulates transcription initiation at most genic promoters and propose a model of initiation site competition to account for this. Together, our results demonstrate that Spt6 controls the fidelity of transcription initiation throughout the genome.

Keywords: Spt6; chromatin structure; intragenic promoters; transcription start sites.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Chromatin / physiology
Gene Expression Regulation, Fungal / genetics
Histone Chaperones / genetics*
Histone Chaperones / metabolism
Histone Chaperones / physiology*
Histones / physiology
Nuclear Proteins
Nucleosomes
Peptide Elongation Factors / physiology
Promoter Regions, Genetic / genetics
RNA Polymerase II
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / genetics*
Saccharomyces cerevisiae Proteins / metabolism
Saccharomyces cerevisiae Proteins / physiology*
Schizosaccharomyces pombe Proteins / genetics
Schizosaccharomyces pombe Proteins / metabolism
Schizosaccharomyces pombe Proteins / physiology
Transcription Factors / physiology
Transcription Initiation Site / physiology
Transcription Initiation, Genetic / physiology*
Transcription, Genetic / genetics
Transcriptional Elongation Factors / genetics*
Transcriptional Elongation Factors / metabolism
Transcriptional Elongation Factors / physiology*

Substances

Chromatin
Histone Chaperones
Histones
Nuclear Proteins
Nucleosomes
Peptide Elongation Factors
SPT6 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Schizosaccharomyces pombe Proteins
Spt6 protein, S pombe
Transcription Factors
Transcriptional Elongation Factors
RNA Polymerase II

Abstract

Publication types

MeSH terms

Substances

Grants and funding