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REVIEWS
M O D E S O F T R A N S C R I P T I O N A L R E G U L AT I O N
Eukaryotic transcriptional dynamics: from single molecules to cell populations
Antoine Coulon1, Carson C.Chow1, Robert H.Singer2,3 and Daniel R.Larson4
Abstract | Transcriptional regulation is achieved through combinatorial interactions between regulatory elements in the human genome and a vast range of factors that modulate the recruitment and activity of RNA polymerase. Experimental approaches for studying transcription invivo now extend from single-molecule techniques to genome-wide measurements. Parallel to these developments is the need for testable quantitative and predictive models for understanding gene regulation. These conceptual models must also provide insight into the dynamics of transcription and the variability that is observed at the single-cell level. In this Review, we discuss recent results on transcriptional regulation and also the models those results engender. We show how a non-equilibrium description informs our view of transcription by explicitly considering time- and energy-dependence at the molecular level.
Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Maryland 20892, USA.
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Janelia Farm Research Campus of the Howard Hughes Medical Institute (HHMI), Ashburn, Virginia 20147, USA.
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Correspondence to D.R.L. e-mail: mailto:[email protected]
Web End [email protected] doi:10.1038/nrg3484 Published online 9 July 2013
Transcriptional regulation in the nucleus is the culmination of the actions of a diverse range of factors, such as transcription factors, chromatin remodellers, polymer-ases, helicases, topoisomerases, kinases, chaperones, proteasomes, acetyltransferases, deacetylases and methyltransferases. Determining how these molecules work in concert in the eukaryotic nucleus to regulate genes remains a central challenge in molecular biology. Dynamics lie at the heart of this mystery. Megadalton complexes assemble and disassemble on genes within seconds1,2; nucleosome turnover ranges from minutes to hours3; and gene activity demonstrates complex temporal patterns such as oscillation and transcriptional bursting4,5. Exciting new experimental advances have enabled the study of dynamic transcriptional regulation at the single-molecule6 and genome-wide7 levels, thus enhancing our understanding of...