title: Dynamics of epigenetic regulation at the single-cell level.
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.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Lacramioara
authors.initials: L
authors.lastname: Bintu
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: John
authors.initials: J
authors.lastname: Yong
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Yaron E
authors.initials: YE
authors.lastname: Antebi
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Kayla
authors.initials: K
authors.lastname: McCue
authors.affiliation: Chromosome Engineering Research Center, Tottori University, 86 Nishicho, Yonago, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kazuki
authors.affiliation: Chromosome Engineering Research Center, Tottori University, 86 Nishicho, Yonago, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Uno
authors.affiliation: Chromosome Engineering Research Center, Tottori University, 86 Nishicho, Yonago, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Howard Hughes Medical Institute (HHMI) and Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA. melowitz@caltech.edu.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Elowitz
mesh_terms: D000107:Acetylation; D000818:Animals; D016466:CHO Cells; D002843:Chromatin / Q000378:metabolism*; D003412:Cricetulus; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D020868:Gene Silencing; D017930:Genes, Reporter; D005818:Genetic Engineering; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008957:Models, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D059010:Single-Cell Analysis; D016335:Zinc Fingers; D000097584:DNA Methyltransferase 3B
chemical_list: D002843:Chromatin; D004248:DNA (Cytosine-5-)-Methyltransferases; D006655:Histone Deacetylases; D006657:Histones; D012097:Repressor Proteins; D000097584:DNA Methyltransferase 3B