A Phase Separation Model for Transcriptional Control

• Published in: Cell Vol. 169; no. 1; pp. 13 - 23
• Main Authors: Hnisz, Denes, Shrinivas, Krishna, Young, Richard A., Chakraborty, Arup K., Sharp, Phillip A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-03-2017
• Subjects: Animals; bursting; co-operativity; enhancer; Enhancer Elements, Genetic; Eukaryotic Cells - metabolism; gene control; Gene Expression Regulation; Humans; Models, Biological; nuclear body; phase separation; super-enhancer; transcription; Transcription Factors - metabolism; Transcription, Genetic; Transcriptional Activation; transcriptional burst; nuclear body; transcriptional burst; enhancer; phase separation; co-operativity; transcription; gene control; bursting; super-enhancer
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2017.02.007

Phase-separated multi-molecular assemblies provide a general regulatory mechanism to compartmentalize biochemical reactions within cells. We propose that a phase separation model explains established and recently described features of transcriptional control. These features include the formation of super-enhancers, the sensitivity of super-enhancers to perturbation, the transcriptional bursting patterns of enhancers, and the ability of an enhancer to produce simultaneous activation at multiple genes. This model provides a conceptual framework to further explore principles of gene control in mammals.
A phase separation model for transcription explains key features of transcription and sets enhancers, and especially super-enhancers, into the broad family of membraneless organelles.