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Dynamics of epigenetic regulation at the single-cell level

Bintu, Lacramioara and Yong, John and Antebi, Yaron E. and McCue, Kayla and Kazuki, Yasuhiro and Uno, Narumi and Oshimura, Mitsuo and Elowitz, Michael B. (2016) Dynamics of epigenetic regulation at the single-cell level. Science, 351 (6274). pp. 720-724. ISSN 0036-8075. PMCID PMC5108652. http://resolver.caltech.edu/CaltechAUTHORS:20160216-093925349

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Abstract

Chromatin regulators play a major role in establishing and maintaining gene expression states. Yet how they control gene expression in single cells, quantitatively and over time, remains unclear. We used time-lapse microscopy to analyze the dynamic effects of four silencers associated with diverse modifications: DNA methylation, histone deacetylation, and histone methylation. For all regulators, silencing and reactivation occurred in all-or-none events, enabling the regulators to modulate the fraction of cells silenced rather than the amount of gene expression. These dynamics could be described by a three-state model involving stochastic transitions between active, reversibly silent, and irreversibly silent states. Through their individual transition rates, these regulators operate over different time scales and generate distinct types of epigenetic memory. Our results provide a framework for understanding and engineering mammalian chromatin regulation and epigenetic memory.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.aab2956DOIArticle
http://science.sciencemag.org/content/351/6274/720PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108652PubMed CentralArticle
ORCID:
AuthorORCID
Elowitz, Michael B.0000-0002-1221-0967
Additional Information:© 2016 American Association for the Advancement of Science. Received 7 April 2015; accepted 1 December 2015. We thank G. M. Abadi, J. Cao, L. Santat, and the Caltech Flow Cytometry Facility for technical assistance and U. Alon, L. Cai, J. Garcia-Ojalvo, A. I. Geraschenko, M. Guttman, B. A. Hay, R. Kishony, A. Moses, R. Phillips, K. Plath, E. Rothenberg, M.-H. Sung, and members of the Elowitz lab for discussions and feedback. This work was supported by the NIH (grants R01 HD075335A and R01 HD075605A to M.B.E.), the Defense Advanced Research Projects Agency (grant W911NF-11-2-0055 to M.B.E.), the Human Frontier Science Program (grant RGP0020/2012 to M.B.E. and Y.E.A.), the Jane Coffin Childs Memorial Fund for Medical Research (postdoctoral fellowship to L.B.), the Beckman Institute at California Institute of Technology (equipment grant to L.B.), the Burroughs Wellcome Fund (Career at the Scientific Interface Award to L.B.), the Gordon and Betty Moore Foundation (through grant GBMF2809 to the Caltech Programmable Molecular Technology Initiative), and HHMI (M.B.E.). M.B.E., L.B., J.Y., and California Institute of Technology filed a provisional patent application (CIT-7162-P) that relates to fractional control devices based on CRs.
Funders:
Funding AgencyGrant Number
NIHR01 HD075335A
NIHR01 HD075605A
Defense Advanced Research Projects Agency (DARPA)W911NF-11-2-0055
Human Frontier Science ProgramRGP0020/2012
Jane Coffin Childs Memorial FundUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
Gordon and Betty Moore FoundationGBMF2809
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
PubMed Central ID:PMC5108652
Record Number:CaltechAUTHORS:20160216-093925349
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20160216-093925349
Official Citation:Dynamics of epigenetic regulation at the single-cell level By Lacramioara Bintu, John Yong, Yaron E. Antebi, Kayla McCue, Yasuhiro Kazuki, Narumi Uno, Mitsuo Oshimura, Michael B. Elowitz Science 12 Feb 2016 : 720-724
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64495
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:17 Feb 2016 22:18
Last Modified:08 Sep 2017 22:41

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