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SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape.
- Source :
-
Molecular cell [Mol Cell] 2021 Nov 04; Vol. 81 (21), pp. 4425-4439.e6. Date of Electronic Publication: 2021 Sep 16. - Publication Year :
- 2021
-
Abstract
- Transcription progression is governed by multitasking regulators including SPT5, an evolutionarily conserved factor implicated in virtually all transcriptional steps from enhancer activation to termination. Here we utilize a rapid degradation system and reveal crucial functions of SPT5 in maintaining cellular and chromatin RNA polymerase II (Pol II) levels. Rapid SPT5 depletion causes a pronounced reduction of paused Pol II at promoters and enhancers, distinct from negative elongation factor (NELF) degradation resulting in short-distance paused Pol II redistribution. Most genes exhibit downregulation, but not upregulation, accompanied by greatly impaired transcription activation, altered chromatin landscape at enhancers, and severe Pol II processivity defects at gene bodies. Phosphorylation of an SPT5 linker at serine 666 potentiates pause release and is antagonized by Integrator-PP2A (INTAC) targeting SPT5 and Pol II, while phosphorylation of the SPT5 C-terminal region links to 3' end termination. Our findings position SPT5 as an essential positive regulator of global transcription.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antigens, Differentiation, B-Lymphocyte
Chromatin chemistry
Chromatin metabolism
Fibroblasts metabolism
Genome
HEK293 Cells
Histocompatibility Antigens Class II
Humans
Mice
Mutation
Phosphorylation
Promoter Regions, Genetic
RNA-Seq
Regulatory Sequences, Nucleic Acid
Transcriptional Activation
Chromosomal Proteins, Non-Histone metabolism
Enhancer Elements, Genetic
Nuclear Proteins metabolism
RNA Polymerase II metabolism
Transcription, Genetic
Transcriptional Elongation Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 81
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 34534457
- Full Text :
- https://doi.org/10.1016/j.molcel.2021.08.029