Dataset Information

Intrinsic dynamics of an endogenous human gene reveal the basis of expression heterogeneity

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. 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE121443 | GEO | 2018/10/29

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:This a model from the article: Calcium and glycolysis mediate multiple bursting modes in pancreatic islets. Bertram R, Satin L, Zhang M, Smolen P, Sherman A. Biophys J2004 Nov;87(5):3074-87 15347584, Abstract: Pancreatic islets of Langerhans produce bursts of electrical activity when exposed to stimulatory glucose levels. These bursts often have a regular repeating pattern, with a period of 10-60 s. In some cases, however, the bursts are episodic, clustered into bursts of bursts, which we call compound bursting. Consistent with this are recordings of free Ca2+ concentration, oxygen consumption, mitochondrial membrane potential, and intraislet glucose levels that exhibit very slow oscillations, with faster oscillations superimposed. We describe a new mathematical model of the pancreatic beta-cell that can account for these multimodal patterns. The model includes the feedback of cytosolic Ca2+ onto ion channels that can account for bursting, and a metabolic subsystem that is capable of producing slow oscillations driven by oscillations in glycolysis. This slow rhythm is responsible for the slow mode of compound bursting in the model. We also show that it is possible for glycolytic oscillations alone to drive a very slow form of bursting, which we call "glycolytic bursting." Finally, the model predicts that there is bistability between stationary and oscillatory glycolysis for a range of parameter values. We provide experimental support for this model prediction. Overall, the model can account for a diversity of islet behaviors described in the literature over the past 20 years. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Bertram R, Satin L, Zhang M, Smolen P, Sherman A. (2004) - version=1.0 The original CellML model was created by: Catherine Lloyd c.lloyd@auckland.ac.nz The University of Auckland This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Dataset Information

Intrinsic dynamics of an endogenous human gene reveal the basis of expression heterogeneity

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure