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Series GSE121443 Query DataSets for GSE121443
Status Public on Oct 29, 2018
Title Intrinsic dynamics of an endogenous human gene reveal the basis of expression heterogeneity
Organism Homo sapiens
Experiment type Other
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. The relationship between these two phenomena and the dynamic regulation of genes in response to upstream signals is unknown. Here, we describe the use of live-cell RNA imaging coupled with Hi-C measurements to dissect the regulation of the estrogen-responsive TFF1 gene under endogenous regulation. Although this gene 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.
Overall design We used 3e HiC to look at the estradiol induced entropy changes for ER bound enhancers.
Contributor(s) Rodriguez J, Ren G, Day CR, Zhao K, Chow CC, Larson DR
Citation(s) 30554876
Submission date Oct 18, 2018
Last update date Jan 28, 2019
Contact name Daniel R Larson
Organization name National Institutes of Health
Street address 41 Medlars Dr
City Bethesda
State/province Maryland
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (6)
GSM3436593 MCF7_0nM_R1: 3e Hi-C human 0 nM MCF7 cell rep.1
GSM3436594 MCF7_0nM_R2: 3e Hi-C human 0 nM MCF7 cell rep.2
GSM3436595 MCF7_0.05nM_R1: 3e Hi-C human 0.05 nM MCF7 cell rep.1
BioProject PRJNA497364
SRA SRP166061

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Supplementary file Size Download File type/resource
GSE121443_chromosome-entropy-100kb.txt.gz 1018.6 Kb (ftp)(http) TXT
GSE121443_enhancer-entropy-1kb.txt.gz 14.8 Kb (ftp)(http) TXT
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