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

Spt6 Is Required for the Fidelity of Promoter Selection.

Author information

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: winston@genetics.med.harvard.edu.

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

PMID:
30318445
PMCID:
PMC6239972
DOI:
10.1016/j.molcel.2018.09.005
[Indexed for MEDLINE]
Free PMC Article

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