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Intrinsic Dynamics of a Human Gene Reveal the Basis of Expression Heterogeneity

Intrinsic Dynamics of a Human Gene Reveal the Basis of Expression Heterogeneity

Joseph Rodriguez, Gang Ren, Christopher R Day, Keji Zhao, Carson C Chow, Daniel R Larson

Cell. 2019 Jan 10;176(1-2):213-226.e18.

PMID: 30554876

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42414470	TFF1 human			Price

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