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

被引：42

作者：

Challal, Drice ^{[1
,2
]}

Barucco, Mara ^{[1
]}

Kubik, Slawomir ^{[3
,4
]}

Feuerbach, Frank ^{[5
]}

Candelli, Tito ^{[6
]}

Geoffroy, Helene ^{[1
]}

Benaksas, Chaima ^{[1
]}

Shore, David ^{[3
,4
]}

Libri, Domenico ^{[1
]}

机构：

[1] Univ Paris Diderot, Sorbonne Paris Cite, Inst Jacques Monod, CNRS,UMR 7592, F-75205 Paris, France

[2] Univ Paris Saclay, Ecole Doctorale Struct & Dynam Syst Vivants, F-91190 Gif Sur Yvette, France

[3] Dept Mol Biol, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland

[4] Inst Genet & Genom Geneva iGe3, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland

[5] CNRS, UMR3525, Inst Pasteur, Paris, France

[6] Princess Maxima Ctr Pediat Oncol, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands

来源：

MOLECULAR CELL | 2018年 / 72卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

BIDIRECTIONAL PROMOTERS; PROTEIN; YEAST; RAP1; GENOME; DNA; ACTIVATION; IDENTIFICATION; DETERMINANTS; ORGANIZATION;

D O I：

10.1016/j.molcel.2018.11.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：955 / +

页数：22

共 52 条

[1]

Azad GK, 2016, FRONT BIOSCI-LANDMRK, V21, P918

[2] A Library of Yeast Transcription Factor Motifs Reveals a Widespread Function for Rsc3 in Targeting Nucleosome Exclusion at Promoters [J].