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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
E-mail(s) fukuyo@chiba-u.jp
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)
GSM4820325 FKBP-SETD1A_HA
GSM4820326 FKBP-SETD1A_BuGZ
GSM4820327 FKBP-SETD1A_BUB3
This SubSeries is part of SuperSeries:
GSE159146 SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia.
Relations
BioProject PRJNA667763
SRA SRP286581

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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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