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Promoter-mediated diversification of transcriptional bursting dynamics following gene duplication

Tunnacliffe, E; Corrigan, AM; Chubb, JR; (2018) Promoter-mediated diversification of transcriptional bursting dynamics following gene duplication. Proceedings of the National Academy of Sciences of the United States of America , 115 (33) pp. 8364-8369. 10.1073/pnas.1800943115. Green open access

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Abstract

During the evolution of gene families, functional diversification of proteins often follows gene duplication. However, many gene families expand while preserving protein sequence. Why do cells maintain multiple copies of the same gene? Here we have addressed this question for an actin family with 17 genes encoding an identical protein. The genes have divergent flanking regions and are scattered throughout the genome. Surprisingly, almost the entire family showed similar developmental expression profiles, with their expression also strongly coupled in single cells. Using live cell imaging, we show that differences in gene expression were apparent over shorter timescales, with family members displaying different transcriptional bursting dynamics. Strong “bursty” behaviors contrasted steady, more continuous activity, indicating different regulatory inputs to individual actin genes. To determine the sources of these different dynamic behaviors, we reciprocally exchanged the upstream regulatory regions of gene family members. This revealed that dynamic transcriptional behavior is directly instructed by upstream sequence, rather than features specific to genomic context. A residual minor contribution of genomic context modulates the gene OFF rate. Our data suggest promoter diversification following gene duplication could expand the range of stimuli that regulate the expression of essential genes. These observations contextualize the significance of transcriptional bursting.

Type: Article
Title: Promoter-mediated diversification of transcriptional bursting dynamics following gene duplication
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.1800943115
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: transcriptional bursting, stochastic gene expression, single cell transcriptomics, Dictyostelium, gene family
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10055694
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