A Phase Separation Model for Transcriptional Control

Denes Hnisz; Krishna Shrinivas; Richard A Young; Arup K Chakraborty; Phillip A Sharp

doi:10.1016/j.cell.2017.02.007

A Phase Separation Model for Transcriptional Control

Cell. 2017 Mar 23;169(1):13-23. doi: 10.1016/j.cell.2017.02.007.

Authors

Denes Hnisz¹, Krishna Shrinivas², Richard A Young³, Arup K Chakraborty⁴, Phillip A Sharp⁵

Affiliations

¹ Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
² Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
³ Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: [email protected].
⁴ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA. Electronic address: [email protected].
⁵ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: [email protected].

Abstract

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.

Keywords: bursting; co-operativity; enhancer; gene control; nuclear body; phase separation; super-enhancer; transcription; transcriptional burst.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Enhancer Elements, Genetic
Eukaryotic Cells / metabolism
Gene Expression Regulation*
Humans
Models, Biological*
Transcription Factors / metabolism
Transcription, Genetic*
Transcriptional Activation

Substances

Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding