@article{oai:shiga-med.repo.nii.ac.jp:00003456,
 author = {辰巳, 剛一 and 河原, 真大 and 木藤, 克之 and 安藤, 朗 and TATSUMI, Goichi and KAWAHARA, Masahiro and YAMAMOTO, Ryusuke and HISHIZAWA, Masakatsu and KITO, Katsuyuki and SUZUKI, Takayoshi and TAKAORI-KONDO, Akifumi and ANDOH, Akira},
 journal = {Leukemia},
 month = {Nov},
 note = {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., Journal Article},
 title = {LSD1-mediated repression of GFI1 super-enhancer plays an essential role in erythroleukemia.},
 year = {2019}
}