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LSD1-mediated repression of GFI1 super-enhancer plays an essential role in erythroleukemia.
http://hdl.handle.net/10422/00012579
http://hdl.handle.net/10422/00012579581ddc00-2ae3-4a81-89c6-08559c394187
名前 / ファイル | ライセンス | アクション |
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s41375-019-0614-6 (7.2 MB)
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© The Author(s), under exclusive licence to Springer Nature Limited 2019
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Supplementary information_s41375-019-0614-6 (1.8 MB)
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© The Author(s), under exclusive licence to Springer Nature Limited 2019
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2019-11-25 | |||||
タイトル | ||||||
タイトル | LSD1-mediated repression of GFI1 super-enhancer plays an essential role in erythroleukemia. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
TATSUMI, Goichi
× TATSUMI, Goichi× KAWAHARA, Masahiro× YAMAMOTO, Ryusuke× HISHIZAWA, Masakatsu× KITO, Katsuyuki× SUZUKI, Takayoshi× TAKAORI-KONDO, Akifumi× ANDOH, Akira |
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著者別名 |
辰巳, 剛一
× 辰巳, 剛一× 河原, 真大× 木藤, 克之× 安藤, 朗 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
書誌情報 |
en : Leukemia 発行日 2019-11-01 |
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出版者 | ||||||
出版者 | Nature Publishing Group | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1476-5551 | |||||
PMID | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | PMID | |||||
関連識別子 | 31676828 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1038/s41375-019-0614-6 | |||||
関連名称 | 10.1038/s41375-019-0614-6 | |||||
権利 | ||||||
権利情報 | © The Author(s), under exclusive licence to Springer Nature Limited 2019 | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
資源タイプ | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal Article |