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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Vydáno v:	Genome Biology Ročník 22; číslo 1; s. 56
Hlavní autoři:	Cavallaro, Massimo, Walsh, Mark D., Jones, Matt, Teahan, James, Tiberi, Simone, Finkenstädt, Bärbel, Hebenstreit, Daniel
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 04.02.2021 Springer Nature B.V BMC
Témata:	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
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1474-760X 1474-7596 1474-760X
DOI:	10.1186/s13059-020-02227-5