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Mol Cell. 2018 Dec 20;72(6):955-969.e7. doi: 10.1016/j.molcel.2018.11.037.

General Regulatory Factors Control the Fidelity of Transcription by Restricting Non-coding and Ectopic Initiation.

Author information

1
Institut Jacques Monod, Centre National de la Recherche Scientifique, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France; Université Paris Saclay, Ecole doctorale Structure et Dynamique des Systèmes Vivants, 91190 Gif sur Yvette, France.
2
Institut Jacques Monod, Centre National de la Recherche Scientifique, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
3
Department of Molecular Biology and Institute of Genetics and Genomics of Geneva (iGe3), 30 quai Ernest-Ansermet, 1211 Geneva 4, Switzerland.
4
Institut Pasteur, Centre National de la Recherche Scientifique, UMR3525 Paris, France.
5
Princess Máxima Center for Pediatric Oncology, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
6
Institut Jacques Monod, Centre National de la Recherche Scientifique, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France. Electronic address: domenico.libri@ijm.fr.

Abstract

The fidelity of transcription initiation is essential for accurate gene expression, but the determinants of start site selection are not fully understood. Rap1 and other general regulatory factors (GRFs) control the expression of many genes in yeast. We show that depletion of these factors induces widespread ectopic transcription initiation within promoters. This generates many novel non-coding RNAs and transcript isoforms with diverse stability, drastically altering the coding potential of the transcriptome. Ectopic transcription initiation strongly correlates with altered nucleosome positioning. We provide evidence that Rap1 can suppress ectopic initiation by a "place-holder" mechanism whereby it physically occludes inappropriate sites for pre-initiation complex formation. These results reveal an essential role for GRFs in the fidelity of transcription initiation and in the suppression of pervasive transcription, profoundly redefining current models for their function. They have important implications for the mechanism of transcription initiation and the control of gene expression.

KEYWORDS:

Abf1; Rap1; Reb1; chromatin remodelers; general regulatory factors; nucleosome depleted regions; nucleosome positioning; pervasive transcription; promoter directionality; transcription initiation fidelity

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