Epigenetic Regulation of the Mammalian Cell
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{"title"=>"Epigenetic regulation of the mammalian cell", "type"=>"journal", "authors"=>[{"first_name"=>"Keith", "last_name"=>"Baverstock", "scopus_author_id"=>"56234815900"}, {"first_name"=>"Mauno", "last_name"=>"R??nkk??", "scopus_author_id"=>"23393842000"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"18523589", "doi"=>"10.1371/journal.pone.0002290", "scopus"=>"2-s2.0-48449102277", "pui"=>"352094537", "sgr"=>"48449102277"}, "id"=>"4fca0652-4a98-38f3-ba84-47abf776809b", "abstract"=>"BACKGROUND: Understanding how mammalian cells are regulated epigenetically to express phenotype is a priority. The cellular phenotypic transition, induced by ionising radiation, from a normal cell to the genomic instability phenotype, where the ability to replicate the genotype accurately is compromised, illustrates important features of epigenetic regulation. Based on this phenomenon and earlier work we propose a model to describe the mammalian cell as a self assembled open system operating in an environment that includes its genotype, neighbouring cells and beyond. Phenotype is represented by high dimensional attractors, evolutionarily conditioned for stability and robustness and contingent on rules of engagement between gene products encoded in the genetic network.\\n\\nMETHODOLOGY/FINDINGS: We describe how this system functions and note the indeterminacy and fluidity of its internal workings which place it in the logical reasoning framework of predicative logic. We find that the hypothesis is supported by evidence from cell and molecular biology.\\n\\nCONCLUSIONS: Epigenetic regulation and memory are fundamentally physical, as opposed to chemical, processes and the transition to genomic instability is an important feature of mammalian cells with probable fundamental relevance to speciation and carcinogenesis. A source of evolutionarily selectable variation, in terms of the rules of engagement between gene products, is seen as more likely to have greater prominence than genetic variation in an evolutionary context. As this epigenetic variation is based on attractor states phenotypic changes are not gradual; a phenotypic transition can involve the changed contribution of several gene products in a single step.", "link"=>"http://www.mendeley.com/research/epigenetic-regulation-mammalian-cell-1", "reader_count"=>29, "reader_count_by_academic_status"=>{"Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Other"=>1, "Student > Master"=>4, "Student > Bachelor"=>4, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Other"=>1, "Student > Master"=>4, "Student > Bachelor"=>4, "Professor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>21, "Medicine and Dentistry"=>3, "Philosophy"=>1, "Physics and Astronomy"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Philosophy"=>{"Philosophy"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1, "Brazil"=>2}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/929645"], "description"=>"<p>Panel A: A relatively small exposure to ionising radiation creates damage in the genomic DNA (red trace) which is detected and repaired by the cell. The prevailing home attractor, H, is perturbed but not irreversibly so, i.e. the basin of attraction is not exceeded and the system stays in the H attractor. Panel B: A larger exposure to ionising radiation but still within the capacity of the cell to repair causes the cell to exceed the basin of attraction of the home attractor, H, and stimulates the irreversible transition to the variant attractor V<sub>1</sub>.</p>", "links"=>[], "tags"=>["responses", "genotypic"], "article_id"=>600099, "categories"=>["Genetics", "Evolutionary Biology"], "users"=>["Keith Baverstock", "Mauno Rönkkö"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002290.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Illustration_of_responses_of_the_system_to_genotypic_damage_/600099", "title"=>"Illustration of responses of the system to genotypic damage.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:17:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/929703"], "description"=>"<p>The figure illustrates a very simplified state space for a two dimension system, the coordinates indicating the activities of gene products x and y. The potential attractors are represented by circles, the diameters of which are proportional to their basins of attraction, the home attractor H being the largest because of environmental conditioning. A perturbation P of H beyond the basin of attraction due to an increase in gene product y causes the adoption of variant attractor V<sub>1</sub>. This is the initiation step of genomic instability. Subsequently, due to the relatively reduced robustness of variant, i.e., unconditioned, attractors, further transitions (dotted lines) to other variant attractors characterises the genomic instability phenotype.</p>", "links"=>[], "tags"=>["Evolutionary biology", "genetics and genomics/epigenetics", "genetics and genomics/gene expression"], "article_id"=>600156, "categories"=>["Genetics", "Evolutionary Biology"], "users"=>["Keith Baverstock", "Mauno Rönkkö"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002290.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Illustration_of_a_state_space_/600156", "title"=>"Illustration of a state space.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:17:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/929765"], "description"=>"<p>The figure illustrates the multi-compartmental dynamic steady state initiated by the transcription of coding sequences to mRNA, which is translated to peptide and finally yields active gene products which are depleted (block arrow) through use. There may be additional depletion (not indicated) by spontaneous decay from the product compartments.</p>", "links"=>[], "tags"=>["multi-compartmental"], "article_id"=>600217, "categories"=>["Genetics", "Evolutionary Biology"], "users"=>["Keith Baverstock", "Mauno Rönkkö"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002290.g003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Illustration_of_the_multi_compartmental_dynamic_steady_state_/600217", "title"=>"Illustration of the multi-compartmental dynamic steady state.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 10:17:48"}

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Relative Metric

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