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SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [RNA-seq]

ABSTRACT: SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [RNA-seq]

PROVIDER: PRJNA667762 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12782744.fastq.gz	Fastqsanger.gz
	SRR12782745.fastq.gz	Fastqsanger.gz
	SRR12782746.fastq.gz	Fastqsanger.gz
	SRR12782747.fastq.gz	Fastqsanger.gz
	SRR24927848.fastq.gz	Fastqsanger.gz

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SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [RNA-seq]

Project description: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.

2023-07-29 | GSE159145 | GEO

SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [ChIP-seq]

2023-07-29 | GSE159144 | GEO

SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia.

Project description:SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia.

| PRJNA667760 | ENA

SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [ChIP-seq]

Project description:SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia [ChIP-seq]

| PRJNA667763 | ENA

SETD1A function in leukemia is mediated through interaction with mitotic regulators BuGZ/BUB3

Project description: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 in and interaction partners of the FLOS domain. Our screen for FLOS domain-binding partners reveals that the SETD1A FLOS domain binds mitosis-associated proteins BuGZ/BUB3. Inhibition of both cyclin K and BuGZ/BUB3 binding motifs in SETD1A shows synergistic anti-leukemic effects. BuGZ/BUB3 localize to SETD1A-bound 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 leukemia cell proliferation. Cell-cycle specific SETD1A restoration assays indicate that SETD1A expression at the G1/S phase of the cell cycle promotes both the expression of DNA damage response genes and cell cycle progression in leukemia cells.

| S-SCDT-10_15252-EMBR_202357108 | biostudies-other

Splicing function of mitotic regulators links R-loop mediated DNA damage to tumor cell killing

Project description:We discovered that two mitotic regulators, BuGZ and Bub3, involved in splicing regulation during interphase

2015-04-11 | GSE67770 | GEO

Splicing function of mitotic regulators links R-loop mediated DNA damage to tumor cell killing

Project description:We discovered that two mitotic regulators, BuGZ and Bub3, involved in splicing regulation during interphase 8 samples from primary Human foreskin fibroblast cells (HFFs) , 12 samples from TOV21G cells. Control siRNA. BuGZ siRNA or Bub3 siRNA were transfected for 48 h before sample collection. Cells treated with pladienolide B served as positive controls. For each RNAi experiment, we had two biological replicates.

2015-04-11 | E-GEOD-67770 | biostudies-arrayexpress

SETD1A function is mediated through interaction with mitotic regulators BuGZ/BUB3 in leukemia.

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-07-29 | GSE159146 | GEO

SETD1A protects from senescence through regulation of the mitotic gene expression program

Project description:SETD1A, a member of the Set1/COMPASS family maintaining H3K4 methylation in the promoters of transcriptionally active genes, is critical for the execution of developmental gene expression and is overexpressed in multiple cancers including breast cancer1-3. Here we show that SETD1A is essential for supporting cellular mitotic processes and consequentially, its depletion leads to senescence. SETD1A directly regulates the expression of several genes orchestrating mitosis and DNA damage responses and its depletion results in multiple mitotic defects including chromosome misalignment and segregation defects. Senescence-associated cell cycle arrest in SETD1A knockdown cells is independent of the mutational status of p53, RB and p16, key mediators of this process, instead, is sustained through direct transcriptional suppression of SKP2, the ubiquitin ligase, which degrades p27 and p21. Rare cells escape senescence and re-enter the cell cycle by restoring SKP2 expression but with enhanced genomic instability. In >200 cancer cell lines and in primary circulating tumor cells, expression of SETD1A correlates with genes involved in mitosis and cell cycle suggesting a role in suppressing senescence induced by aberrant mitosis. Thus, SETD1A encodes a chromatin modifier, whose modulation may maintain the balance between senescence and genomic instability in cells.

2019-07-08 | GSE117427 | GEO

Epigenetic modification of GR enhancers by SETD1A/COMPASS complex in murine macrophages

Project description:Nuclear interaction studies by ChIP coupled with mass spectrometry identified the COMPASS/SETD1A complex as interaction partner of the glucocorticoid receptor (GR) in murine bone marrow-derived macrophages (BMDMs). Here, we profiled the occupancy of SETD1A and CXXC1, two subunits of the COMPASS/SETD1A complex in murine macrophages after LPS and Dex+LPS stimulation. We show, that GR recuits SETD1A and CXXC1 to GR enhancer and that SETD1A recruitment does correlate with changes in H3K4methylation at some of those enhancers.

2020-12-31 | GSE136070 | GEO

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