Publication Date:
2016-02-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bintu, Lacramioara -- Yong, John -- Antebi, Yaron E -- McCue, Kayla -- Kazuki, Yasuhiro -- Uno, Narumi -- Oshimura, Mitsuo -- Elowitz, Michael B -- R01 HD075335A/HD/NICHD NIH HHS/ -- R01 HD075605A/HD/NICHD NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):720-4. doi: 10.1126/science.aab2956.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. ; Chromosome Engineering Research Center, Tottori University, 86 Nishicho, Yonago, Japan. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912859" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylation
;
Animals
;
CHO Cells
;
Chromatin/*metabolism
;
Cricetulus
;
DNA (Cytosine-5-)-Methyltransferase/metabolism
;
*DNA Methylation
;
*Gene Silencing
;
Genes, Reporter
;
Genetic Engineering
;
Histone Deacetylases/metabolism
;
Histones/*metabolism
;
Humans
;
Models, Genetic
;
Repressor Proteins/metabolism
;
Single-Cell Analysis
;
Zinc Fingers
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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