{"created":"2023-05-15T10:01:16.167054+00:00","id":5787,"links":{},"metadata":{"_buckets":{"deposit":"5f8e374c-a9b1-4b72-b1c3-74627da62979"},"_deposit":{"created_by":5,"id":"5787","owner":"5","owners":[5],"pid":{"revision_id":0,"type":"depid","value":"5787"},"status":"published"},"_oai":{"id":"oai:miyazaki-u.repo.nii.ac.jp:00005787","sets":["72","72:38"]},"author_link":["4839","23623"],"item_10010_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"In this article we review our recent studies on the ability of higher eukaryotes for gaining un-programmed and new cell functions by means of irreversible creation of chromatin structure plasticity through various generations. Following the ways to diminish IgM H- and L-chains excessively accumulated in histone deacetylase-2 （HDAC2）-deficient DT40 mutants HDAC2（-/-） as a concrete case, we proposed a universal hypothetic concept on the ability of higher eukaryotic cells to adapt to abnormal and/or uncomfortable environment changes. In chicken wild-type DT40 cells, HDAC2 as a supervisor indirectly regulates gene expressions of IgM H- and L-chains through opposite regulations of gene expressions of Pax5, Aiolos, EBF1, OBF1, and Ikaros plus E2A. The HDAC2-deficiency rapidly induces dramatic accumulations of mRNAs and proteins of IgM H- and L-chains, and thereafter these accumulated mRNAs and proteins are dramatically reduced in almost similar changing pattern in all individual clones of HDAC2（-/-） DT40 mutants during simple continuous cultivation under the same conditions. By contrast, gene expressions of Pax5, Aiolos, EBF1 and OBF1 remarkably show distinct changing patterns in individual clones of HDAC2（-/-） mutants during the same simple continuous cultivation. At the later stage of cultivation, there exist at least three distinct ways for gene expressions of IgM H- and L-chains, i.e., OBF1-dependent, Pax5- plus Aiolos-dependent, and Pax5-, Aiolos- plus EBF1-dependent types. The complicated alterations in gene expressions of Pax5, Aiolos, EBF1 and OBF1 in individual clones of HDAC2（-/-） mutants are based on varied irreversible chromatin conformation （structure） changes attributed to diverse changes in acetylation and/or deacetylation levels of specific Lys residues of histone H3 within their proximal 5'-upstream chromatin regions during continuous cultivation. Based on these results, we proposed a universal concept, which we named the chromatin conformation change code （4C） theory, for a bio-system to gain un-programmed and new cell functions by means of irreversible creation of chromatin structure plasticity with epigenetic modifications through various generations.\n Outline of the 4C theory, which is one of the most fundamental and important ways for life conservation and cell type determination of higher eukaryotes, is concretely as follows. 1） Somatic cells of higher eukaryotes are pluri-potent, elastic and flexible to gain un-programmed and new cell functions to cope with and/or overcome new environment change, when they firstly encounter with it in their lives. 2） The pluri-potency, elasticity and flexibility are basically originated from those of the chromatin structure. 3） Somatic cells gradually acquire the ability to gain un-programmed and new cell functions to adapt to and/or eliminate the environment change by means of irreversible creation of chromatin structure plasticity surrounding the proximal 5'-upstream region（s） of specific transcription factor and chromatin-modifying enzyme genes through various generations （cell divisions）. 4） Chromatin structure plasticity （from the tight to loose forms or vice versa） is continuously and irreversibly created based on the chromatin conformation change with epigenetic modifications through various generations. 5） Diversity of chromatin structure plasticity in individual cells of the same type is triggered by spontaneous unbalanced response to the environment change and accomplished by its successive convergence through various generations. 6） Irreversible creation of chromatin structure plasticity depends on antecedents of somatic cells and successive response to the environment change. 7） Irreversible creation of chromatin structure plasticity occurs in descendent cells but not in the cell which initially meets with the environment change. 8） Irreversible creation of chromatin structure plasticity probably occurs inevitably but not incidentally and/or neutrally. 9） The environment change is recognized by putative environment change recognition receptor/site （ECRR/ECRS）, and chromatin structure plasticity is irreversibly and directly created by putative chromatin conformation change complex （4C） machinery. 10） The chromatin structure of the proximal 5'-upstream region（s） of the specific gene（s）, as dynamic and changeable three-dimensional conformation, receives signal on the environment change. 11） The chromatin structure （the loose or tight form） of the proximal 5'-upstream region of the specific gene directs the switch （on or off） for its latent gene expression ability. 12） The proximal 5'-upstream chromatin region of the specific gene is regarded as “notch of chromatin\" from a structural point of view and “director for gene expression\" from a functional point of view. 13） The supposed number of codes in the 4C theory, which determines complicated cell functions and diverse cell types in higher eukaryotes, may be estimated based on combination of the number of candidate genes and that （probably two） of codes for each of these specific candidate genes.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10010_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"中山, 建男","creatorNameLang":"ja"},{"creatorName":"ナカヤマ, タツオ","creatorNameLang":"ja-Kana"},{"creatorName":"Nakayama, Tatsuo","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"4839","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"中山, 雅美","creatorNameLang":"ja"},{"creatorName":"ナカヤマ, マサミ","creatorNameLang":"ja-Kana"},{"creatorName":"Nakayama, Masami","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"23623","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-06-21"}],"displaytype":"detail","filename":"1-1-text.pdf","filesize":[{"value":"511.2 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"text","url":"https://miyazaki-u.repo.nii.ac.jp/record/5787/files/1-1-text.pdf"},"version_id":"ab03c001-31d8-4fd7-984e-97a182d47866"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-02-16"}],"displaytype":"detail","filename":"1-Supplementary Remarks.pdf","filesize":[{"value":"61.5 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Supplementary Remarks","url":"https://miyazaki-u.repo.nii.ac.jp/record/5787/files/1-Supplementary 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kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"fig22","url":"https://miyazaki-u.repo.nii.ac.jp/record/5787/files/fig-22.pdf"},"version_id":"22634134-a74e-427e-ae30-7703abd9536a"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-06-21"}],"displaytype":"detail","filename":"fig-23.pdf","filesize":[{"value":"74.7 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"fig23","url":"https://miyazaki-u.repo.nii.ac.jp/record/5787/files/fig-23.pdf"},"version_id":"30e13c39-6af2-47d2-bb9d-7ec3b0a9b583"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Gene targeting techniques, chicken DT40 cells, histone deacetylase-2 (HDAC2), HDAC2-deficient DT40 mutants (HDAC2(-/-)), IgM H- and L-chains, continuous cultivation, various generations, decreases in IgM H- and L-chain protein and mRNA levels, changes in mRNA levels of Pax5, Aiolos, EBF1, OBF1 genes in individual mutant clones, irreversible creation of chromatin structure plasticity, proximal 5'-upstream chromatin regions of Pax5, EBF1 and OBF1 genes, alterations in acetylation and deacetylation levels of K9/H3, K14/H3, K19/H3, K23/H3 and K27/H3, epigenetic modifications, neighboring overlapping tailing chromatin immuno-precipitation (NotchIP) assay, environment change recognition receptor/site (ECRR/ECRS), chromatin conformation change complex (4C) machinery, chromatin conformation change code (4C) theory, gaining un-programmed and new cell function(s), pluri-potency, elasticity and flexibility of somatic cells of higher eukaryotes","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"other","resourceuri":"http://purl.org/coar/resource_type/c_1843"}]},"item_title":"A comprehensive review on the chromatin conformation change code (4C) theory: A bio-system for gaining un-programmed and new cell functions by means of irreversible creation of chromatin structure plasticity with epigenetic modifications through various generations in higher eukaryotes","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"A comprehensive review on the chromatin conformation change code (4C) theory: A bio-system for gaining un-programmed and new cell functions by means of irreversible creation of chromatin structure plasticity with epigenetic modifications through various generations in higher eukaryotes","subitem_title_language":"en"}]},"item_type_id":"10010","owner":"5","path":["72","38"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2020-06-21"},"publish_date":"2020-06-21","publish_status":"0","recid":"5787","relation_version_is_last":true,"title":["A comprehensive review on the chromatin conformation change code (4C) theory: A bio-system for gaining un-programmed and new cell functions by means of irreversible creation of chromatin structure plasticity with epigenetic modifications through various generations in higher eukaryotes"],"weko_creator_id":"5","weko_shared_id":2},"updated":"2024-01-30T04:24:14.467545+00:00"}