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    Dynamics of epigenetic regulation at the single-cell level (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    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
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Design principles of cell circuits with paradoxical components (2012)
    National Academy of Sciences
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    Publication Date: 2012-05-04
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Cell circuits with paradoxical components [Systems Biology] (2012)
    National Academy of Sciences
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    Publication Date: 2012-05-23
    Description: Biological systems display complex networks of interactions both at the level of molecules inside the cell and at the level of interactions between cells. Networks of interacting molecules, such as transcription networks, have been shown to be composed of recurring circuits called network motifs, each with specific dynamical functions. Much less is known about the possibility of such circuit analysis in networks made of communicating cells. Here, we study models of circuits in which a few cell types interact by means of signaling molecules. We consider circuits of cells with architectures that seem to recur in immunology. An intriguing feature of these circuits is their use of signaling molecules with a pleiotropic or paradoxical role, such as cytokines that increase both cell growth and cell death. We find that pleiotropic signaling molecules can provide cell circuits with systems-level functions. These functions include for different circuits maintenance of homeostatic cell concentrations, robust regulation of differentiation processes, and robust pulses of cells or cytokines.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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