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Series GSE159144 Query DataSets for GSE159144
Status Public on Jul 29, 2023
Title SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The H3K4 methyltransferase SETD1A plays a crucial role in leukemia cell survival through its non-catalytic FLOS domain mediated recruitment of cyclin K and regulation of DNA damage response genes. In this study, we identify a functional nuclear localization signal and interaction partners for the FLOS domain. Our proteomics analysis against FLOS domain-binding partners reveals that the SETD1A FLOS domain binds mitosis-associated proteins BuGZ/BUB3. Targeted inhibition of both cyclin K and BuGZ/BUB3 binding motifs on SETD1A shows synergistic anti-leukemic effects. BuGZ/BUB3 localize to SETD1A-positive promoter-TSS regions and SETD1A-negative H3K4me1-positive enhancer regions adjacent to SETD1A-target genes. The GLEBS motif and intrinsically disordered region of BuGZ are required for both SETD1A binding and the leukemia cell proliferation. Despite the role of BuGZ/BUB3 at mitotic phase, the cell-cycle specific SETD1A restoration study indicates the roles of SETD1A at G1/S phase of cell cycle. Discovery of this complex indicates the indispensable role of the SETD1A-BuGZ axis in cancer.
Overall design 1) Examination of SETD1A, BuGZ and BUB3 targets in human MOLM-13 leukemia cell line,
2) Examination of BuGZ and SETD1A knockdown in human MOLM-13 leukemia cell line.
3) Examination of SETD1A knockout and rescue in mouse MLL-AF9 leukemia cell line.
Contributor(s) Hoshii T, Perlee S, Kikuchi S, Rahmutulla B, Fukuyo M, Kaneda A
Citation(s) 37535603
Submission date Oct 06, 2020
Last update date Oct 29, 2023
Contact name Masaki Fukuyo
Organization name Chiba University
Department Department of Molecular Oncology
Street address 1-8-1 Inohana, Chuo-ku
City Chiba
ZIP/Postal code 260-8670
Country Japan
Platforms (2)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (5)
This SubSeries is part of SuperSeries:
GSE159146 SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia.
BioProject PRJNA667763
SRA SRP286581

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Supplementary file Size Download File type/resource
GSE159144_RAW.tar 584.8 Mb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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