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Published February 12, 2016 | Accepted Version + Supplemental Material
Journal Article Open

Dynamics of epigenetic regulation at the single-cell level


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.

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.

Attached Files

Accepted Version - nihms825209.pdf

Supplemental Material - Bintu.SM.pdf

Supplemental Material - aab2956s1.mp4

Supplemental Material - aab2956s10.mp4

Supplemental Material - aab2956s11.mp4

Supplemental Material - aab2956s12.mp4

Supplemental Material - aab2956s13.avi

Supplemental Material - aab2956s14.avi

Supplemental Material - aab2956s15.avi

Supplemental Material - aab2956s16.avi

Supplemental Material - aab2956s2.mp4

Supplemental Material - aab2956s3.mp4

Supplemental Material - aab2956s4.mp4

Supplemental Material - aab2956s5.avi

Supplemental Material - aab2956s6.avi

Supplemental Material - aab2956s7.avi

Supplemental Material - aab2956s8.avi

Supplemental Material - aab2956s9.mp4


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August 20, 2023
October 17, 2023