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Mol Cell. 2018 Dec 6;72(5):875-887.e9. doi: 10.1016/j.molcel.2018.09.009. Epub 2018 Oct 11.

Single-Molecule Analysis Reveals Linked Cycles of RSC Chromatin Remodeling and Ace1p Transcription Factor Binding in Yeast.

Author information

1
CCR/LRBGE Optical Microscopy Core, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
2
Division of Developmental Biology, Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
3
Institute for Soft Matter and Functional Materials, Helmholtz Center Berlin, Berlin 12489, Germany.
4
CCR/LRBGE Optical Microscopy Core, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: karpovat@mail.nih.gov.

Abstract

It is unknown how the dynamic binding of transcription factors (TFs) is molecularly linked to chromatin remodeling and transcription. Using single-molecule tracking (SMT), we show that the chromatin remodeler RSC speeds up the search process of the TF Ace1p for its response elements (REs) at the CUP1 promoter. We quantified smFISH mRNA data using a gene bursting model and demonstrated that RSC regulates transcription bursts of CUP1 only by modulating TF occupancy but does not affect initiation and elongation rates. We show by SMT that RSC binds to activated promoters transiently, and based on MNase-seq data, that RSC does not affect the nucleosomal occupancy at CUP1. Therefore, transient binding of Ace1p and rapid bursts of transcription at CUP1 may be dependent on short repetitive cycles of nucleosome mobilization. This type of regulation reduces the transcriptional noise and ensures a homogeneous response of the cell population to heavy metal stress.

KEYWORDS:

ACE1; CUP1; RSC complex; Saccharomyces cerevisiae; chromatin remodeling; single molecule tracking; smFISH; transcription bursts; transcription factors; transient binding

PMID:
30318444
PMCID:
PMC6289719
[Available on 2019-12-06]
DOI:
10.1016/j.molcel.2018.09.009
[Indexed for MEDLINE]

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