DNA residence time is a regulatory factor of transcription repression

Karen Clauß, Achim P. Popp, Lena Schulze, Johannes Hettich, Matthias Reisser, Laura Escoter Torres, N. Henriette Uhlenhaut, J. Christof M. Gebhardt

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

35 Zitate (Scopus)

Abstract

Transcription comprises a highly regulated sequence of intrinsically stochastic processes, resulting in bursts of transcription intermitted by quiescence. In transcription activation or repression, a transcription factor binds dynamically to DNA, with a residence time unique to each factor. Whether the DNA residence time is important in the transcription process is unclear. Here, we designed a series of transcription repressors differing in their DNA residence time by utilizing the modular DNA binding domain of transcription activator-like effectors (TALEs) and varying the number of nucleotide-recognizing repeat domains. We characterized the DNA residence times of our repressors in living cells using single molecule tracking. The residence times depended non-linearly on the number of repeat domains and differed by more than a factor of six. The factors provoked a residence time-dependent decrease in transcript level of the glucocorticoid receptor-Activated gene SGK1. Down regulation of transcription was due to a lower burst frequency in the presence of long binding repressors and is in accordance with a model of competitive inhibition of endogenous activator binding. Our single molecule experiments reveal transcription factor DNA residence time as a regulatory factor controlling transcription repression and establish TALE-DNA binding domains as tools for the temporal dissection of transcription regulation.

OriginalspracheEnglisch
Seiten (von - bis)11121-11130
Seitenumfang10
FachzeitschriftNucleic Acids Research
Jahrgang45
Ausgabenummer19
DOIs
PublikationsstatusVeröffentlicht - 2 Nov. 2017
Extern publiziertJa

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