Biophysical Society Thematic Meeting| Lima 2019

Revisiting the Central Dogma of Molecular Biology at the Single-Molecule Level

Poster Abstracts

25-POS Board 25 SINGLE MOLECULE TRACKING REVEALS FAST INTERDEPENDENT CYCLING OF TRANSCRIPTION FACTOR ACE1P AND CHROMATIN REMODELER RSC AT CUP1 PROMOTER IN YEAST Gunjan D Mehta 1 ; David A Ball 1 ; Tatiana S. Karpova 1 ; 1 NIH/National Cancer Institute, LRBGE/Optical Microscopy Core, Bethesda, MD, USA We investigate the molecular links between the dynamic binding of Transcription Factors (TF) and chromatin remodeling and transcription. For several TFs their residence time at the specific sites is critical for the regulation of transcription and increase in residence time improves the transcriptional output. RSC chromatin remodeler affects the transcription of the yeast metallothionein-encoding CUP1. Using Single Molecule Tracking, we show that the chromatin remodeler RSC decreases the residence time of the TF, and speeds up the search process of the TF Ace1p for its Response Elements (RE) at the CUP1 promoter. We quantify smFISH CUP1 mRNA data using a gene bursting model, and demonstrate that RSC regulates transcription bursts of CUP1 by modulating TF occupancy. We show by SMT that RSC binds to activated promoters transiently. 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

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