3 ′-5 ′ crosstalk contributes to transcriptional bursting

Background Transcription in mammalian cells is a complex stochastic process involving shuttling of polymerase between genes and phase-separated liquid condensates. It occurs in bursts, which results in vastly different numbers of an mRNA species in isogenic cell populations. Several factors contribu...

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Bibliographic Details
Published in:Genome Biology Vol. 22; no. 1; p. 56
Main Authors: Cavallaro, Massimo, Walsh, Mark D., Jones, Matt, Teahan, James, Tiberi, Simone, Finkenstädt, Bärbel, Hebenstreit, Daniel
Format: Journal Article
Language:English
Published: London BioMed Central 04.02.2021
Springer Nature B.V
BMC
Subjects:
Animal Genetics and Genomics
Animals
Bayes Theorem
Bayesian analysis
Bayesian theory
beta-Globins - genetics
Bioinformatics
Biological noise
Biomedical and Life Sciences
Burst size
Cell cycle
Cell Physiological Phenomena
Evolutionary Biology
Gene Expression
Gene looping
Genomes
HEK293 Cells
Human Genetics
Humans
Life Sciences
Liquid-liquid phase separation
liquids
Mammalian cells
mammals
Mathematical modelling
Microbial Genetics and Genomics
Models, Genetic
Models, Theoretical
Morphology
Mutation
Parameter inference
Plant Genetics and Genomics
RNA polymerase
RNA, Messenger
Stochastic Processes
transcription (genetics)
Transcription factors
Transcription termination
Transcription, Genetic
Transgenes
Mathematical modelling
Liquid-liquid phase separation
Gene expression
Gene looping
Parameter inference
Biological noise
ISSN:1474-760X, 1474-7596, 1474-760X
Online Access:Get full text
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Summary:Background Transcription in mammalian cells is a complex stochastic process involving shuttling of polymerase between genes and phase-separated liquid condensates. It occurs in bursts, which results in vastly different numbers of an mRNA species in isogenic cell populations. Several factors contributing to transcriptional bursting have been identified, usually classified as intrinsic, in other words local to single genes, or extrinsic, relating to the macroscopic state of the cell. However, some possible contributors have not been explored yet. Here, we focus on processes at the 3 ′ and 5 ′ ends of a gene that enable reinitiation of transcription upon termination. Results Using Bayesian methodology, we measure the transcriptional bursting in inducible transgenes, showing that perturbation of polymerase shuttling typically reduces burst size, increases burst frequency, and thus limits transcriptional noise. Analysis based on paired-end tag sequencing (PolII ChIA-PET) suggests that this effect is genome wide. The observed noise patterns are also reproduced by a generative model that captures major characteristics of the polymerase flux between the ends of a gene and a phase-separated compartment. Conclusions Interactions between the 3 ′ and 5 ′ ends of a gene, which facilitate polymerase recycling, are major contributors to transcriptional noise.
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ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-020-02227-5