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| Status |
Public on Jul 29, 2023 |
| Title |
SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [RNA-seq] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| 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.
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| 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
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| City |
Chiba |
| ZIP/Postal code |
260-8670 |
| Country |
Japan |
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| Platforms (2) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE159146 |
SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia. |
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| Relations |
| BioProject |
PRJNA667762 |
| SRA |
SRP286580 |
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