The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
Intrinsic Dynamics of a Human Gene Reveal the Basis of Expression Heterogeneity
Open accessAbstract
Summary Transcriptional regulation in metazoans occurs through long range genomic contacts between enhancers and promoters, and most genes are transcribed in episodic ‘bursts’ of RNA synthesis. To understand the relationship between these two phenomena and the dynamic regulation of genes in response to upstream signals, we describe the use of live-cell RNA imaging coupled with Hi-C measurements and dissect the endogenous regulation of the estrogen-responsive TFF1 gene. Although TFF1 is highly induced, we observe short active periods and variable inactive periods ranging from minutes to days. The heterogeneity in inactive times gives rise to the widely-observed ‘noise’ in human gene expression and explains the distribution of protein levels in human tissue. We derive a mathematical model of regulation that relates transcription, chromosome structure, and the cell’s ability to sense changes in estrogen and predicts that hypervariability is largely dynamic and does not reflect a stable biological state.
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Metadata
- Authors
- Rodriguez, J., Ren, G., Day, C. R., Zhao, K., Chow, C. C., & Larson, D. R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 176
- Issue
- 1-2
- Pages
- 213-226.e18
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2904827199
- Cited by
- 265
- References
- 72
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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