{"created":"2023-06-19T10:43:15.411689+00:00","id":3456,"links":{},"metadata":{"_buckets":{"deposit":"f499875f-0e22-4e6e-bb1d-0a6aee6e2834"},"_deposit":{"created_by":11,"id":"3456","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"3456"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00003456","sets":["30:227:228"]},"author_link":["7633","314","7509","7636","7637","644","7634","7635"],"item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-11-01","bibliographicIssueDateType":"Issued"},"bibliographic_titles":[{},{"bibliographic_title":"Leukemia","bibliographic_titleLang":"en"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"辰巳, 剛一"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"河原, 真大"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"木藤, 克之"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"安藤, 朗"}],"nameIdentifiers":[{},{},{}]}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Super-enhancers (SEs) consist of enhancer clusters with abundant binding of transcription factors (TFs) and cofactors. LSD1 is a histone modifier that eliminates SE activity. However, whether SE suppression by LSD1 is associated with leukemogenesis remains unknown. In erythro-megakaryocyte lineage leukemia cells, activation of the SE of GFI1 (GFI1-SE) is related to induction of myeloid differentiation by LSD1 inhibitors NCD38 and NCD25 and to their antileukemia effect. Although functional TF-motifs were concentrated in an evolutionally conserved area, NCD38 barely induced additional TF recruitment. Instead, the transcription cofactors including LSD1, CoREST, HDAC1, and HDAC2 were evicted from GFI1-SE. Deletion of GFI1-SE impaired induction of myeloid differentiation by NCD38 and NCD25 in erythroleukemia cells. Gene set enrichment analysis revealed that the GFI1-SE deletion impaired NCD38-induced programs related to granulocyte differentiation and the CEBPA network, but restored NCD38-suppressed programs related to erythroid development, GATA1 targets, and acute myeloid leukemia (AML) clusters including FAB subtype M6 and AML with myelodysplastic syndrome-related chromosomal abnormalities. Ontologies of genes whose expression changes by NCD38 were canceled due to the GFI1-SE deletion showed enrichment in AML and neutropenia signatures. Collectively, our data suggest that sustainable repression of GFI1-SE by LSD1 is essential for sustenance of erythroleukemia cells.","subitem_description_type":"Abstract"}]},"item_4_description_42":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Journal Article","subitem_description_type":"Other"}]},"item_4_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Nature Publishing Group"}]},"item_4_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"31676828","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"10.1038/s41375-019-0614-6"}],"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1038/s41375-019-0614-6","subitem_relation_type_select":"DOI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© The Author(s), under exclusive licence to Springer Nature Limited 2019"}]},"item_4_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1476-5551","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_15":{"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":"TATSUMI, Goichi"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"KAWAHARA, Masahiro"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"YAMAMOTO, Ryusuke"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"HISHIZAWA, Masakatsu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"KITO, Katsuyuki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"SUZUKI, Takayoshi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"TAKAORI-KONDO, Akifumi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"ANDOH, Akira"}],"nameIdentifiers":[{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-05-01"}],"displaytype":"detail","filename":"s41375-019-0614-6.pdf","filesize":[{"value":"7.2 MB"}],"format":"application/pdf","license_note":"© The Author(s), under exclusive licence to Springer Nature Limited 2019","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"s41375-019-0614-6","url":"https://shiga-med.repo.nii.ac.jp/record/3456/files/s41375-019-0614-6.pdf"},"version_id":"69a0075d-9e23-4db2-9623-c2069f66ad79"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-05-01"}],"displaytype":"detail","filename":"Supplementary information_s41375-019-0614-6.pdf","filesize":[{"value":"1.8 MB"}],"format":"application/pdf","license_note":"© The Author(s), under exclusive licence to Springer Nature Limited 2019","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Supplementary information_s41375-019-0614-6","url":"https://shiga-med.repo.nii.ac.jp/record/3456/files/Supplementary information_s41375-019-0614-6.pdf"},"version_id":"8a288505-1e72-4398-b0ba-1ceaddfaa18b"}]},"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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"LSD1-mediated repression of GFI1 super-enhancer plays an essential role in erythroleukemia.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"LSD1-mediated repression of GFI1 super-enhancer plays an essential role in erythroleukemia."}]},"item_type_id":"4","owner":"11","path":["228"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-11-25"},"publish_date":"2019-11-25","publish_status":"0","recid":"3456","relation_version_is_last":true,"title":["LSD1-mediated repression of GFI1 super-enhancer plays an essential role in erythroleukemia."],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-06-19T12:24:38.231842+00:00"}