Effect of SETD1A knockdown on global gene expression in MCF-7 cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE101860 | GEO | 2018/10/24
REPOSITORIES: GEO
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Project description:Investigation of gene expression level changes in the SETD1A depleted cancer cells (shSETD1A), compared to the GFP depleted cancer cells (shGFP) as control. This analysis was performed to gain an understanding of the transcriptional changes induced by chromation modifications through H3K4 methyltransferase SETD1A. Key Word: SETD1A, Epigenetics
2017-07-18 | GSE71498 | GEO
Project description:As Setd1a is a methyltransferase targeting H3K4, we performed H3K4Me3 ChIP in control and Setd1a KO cell to observe the effects of Setd1a on H3K4Me3. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for H3K4Me in control mouse UPS and Setd1a KO mouse UPS cells .
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Project description:The human HOTAIR-specific siRNA and control siRNA were transfected into MCF-7-TNR cells. RNA was collected at 72 hrs after transfection. RNA-SEQ was carried out to profile the gene expression altered by HOTAIR knockdown.
2019-01-11 | GSE124934 | GEO
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
Project description:We investigated the functions/pathways affected by SPEN knockdown in breast cancer by global expression profiling in a cell model, where the human breast cancer cell line, MCF-7, were transfected with an shRNA targeting SPEN mRNA.
2015-10-21 | E-MTAB-2183 | biostudies-arrayexpress
Project description:Homologous recombination-mediated DNA repair deficiency (HRD) predisposes to cancer development, but also provides therapeutic opportunities Here, we identified an HRD gene signature that robustly predicted HRD status Unexpectedly, concurrent loss of PTEN in BRCA1-deficient cells might extensively rewire the HR repair network and confer resistance to PARP inhibitor, partially through over-expression of TTK We used the HRD gene signature as a drug discovery tool and found several PARP-inhibitor-synergizing agents through the connectivity map Thus gene expression profiling can be used to define the functional status of the HR repair network providing prognostic and therapeutic information Various shRNAs that target genes involved in homologous recombination (HR) were transfected in MCF-10A non-transformed breast cells lines Stable HR gene knockdown MCF-10A cells were seeded 200000 at 10 cm plate Cells were harvested after 48 hours culturing and used for gene expression profiling The shRNA that target Brit1 genes was transfected in MCF-10A non-transformed breast cell line by lentiviral particles and selected stable Brit1 knockdown MCF-10A cells. Scrambled control shRNA-transfected MCF-10A cells were applying as control. Both stable Brit1 knockdown and control MCF-10A cells were seeded with 2 x 10^5 cells at 10 cm culture plate. Cells were cultured in MCF-10A medium and harvested after 48 hours culturing. mRNA was extracted from collected cells and performing gene expression profiling. Three or four biological replicates were applied.
2014-01-24 | E-GEOD-54264 | biostudies-arrayexpress
Project description:The H3K4 methyltransferase SETD1A plays an essential role in both development and cancer. However, essential components involved in SETD1A chromatin binding remain unclear. Here, we discovered that BOD1L exhibits the highest correlated co-dependency with SETD1A in human cancer cell lines. BOD1L knockout reduces leukemia cells in vitro and in vivo, and mimics the transcriptional profiles observed in SETD1A knockout cells. The loss of BOD1L immediately reduced SETD1A distribution at transcriptional start sites (TSS) and induces transcriptional elongation defect along with the increasing of RNA polymerase II at TSS, but did not cause the reduction of H3K4me3. The Shg1 domain of BOD1L has a DNA binding ability, and recruit SETD1A to chromatin through the association with SETD1A FLOS domain. In addition, the BOD1L-SETD1A complex associates with transcriptional regulators, including E2Fs. These results reveal that BOD1L mediates chromatin and SETD1A, and regulates the non-canonical function of SETD1A in transcription.
2024-06-25 | GSE258789 | GEO
Project description:The H3K4 methyltransferase SETD1A plays an essential role in both development and cancer. However, essential components involved in SETD1A chromatin binding remain unclear. Here, we discovered that BOD1L exhibits the highest correlated co-dependency with SETD1A in human cancer cell lines. BOD1L knockout reduces leukemia cells in vitro and in vivo, and mimics the transcriptional profiles observed in SETD1A knockout cells. The loss of BOD1L immediately reduced SETD1A distribution at transcriptional start sites (TSS) and induces transcriptional elongation defect along with the increasing of RNA polymerase II at TSS, but did not cause the reduction of H3K4me3. The Shg1 domain of BOD1L has a DNA binding ability, and recruit SETD1A to chromatin through the association with SETD1A FLOS domain. In addition, the BOD1L-SETD1A complex associates with transcriptional regulators, including E2Fs. These results reveal that BOD1L mediates chromatin and SETD1A, and regulates the non-canonical function of SETD1A in transcription.
2024-06-25 | GSE258788 | GEO
Project description:Homologous recombination-mediated DNA repair deficiency (HRD) predisposes to cancer development, but also provides therapeutic opportunities. Here, we identified an HRD gene signature that robustly predicted HRD status. Unexpectedly, concurrent loss of PTEN in BRCA1-deficient cells might extensively rewire the HR repair network and confer resistance to PARP inhibitor, partially through over-expression of TTK. We used the HRD gene signature as a drug discovery tool and found several PARP-inhibitor-synergizing agents through the connectivity map. Thus gene expression profiling can be used to define the functional status of the HR repair network providing prognostic and therapeutic information. Various shRNAs that target genes involved in homologous recombination (HR) were transfected in MCF-10A non-transformed breast cells lines. Stable HR gene knockdown MCF-10A cells were seeded 200000 at 10 cm plate. Cells were harvested after 48 hours culturing and used for gene expression profiling. The shRNAs that target PTEN or BRCA1 genes were transfected in MCF-10A non-transformed breast cell line by lentiviral particles. Stable BRCA1 and PTEN knockdown MCF-10A cells were selected. Scrambled control shRNA-transfected MCF-10A cells were applying as control. All knockdown and control MCF-10A cells were seeded with 2 x 10^5 cells at 10 cm culture plate. Cells were cultured in MCF-10A medium and harvested after 48 hours culturing. mRNA was extracted from collected cells and performing gene expression profiling. Four biological replicates were applied. Four biological replicates were applied.
2014-01-24 | E-GEOD-54266 | biostudies-arrayexpress
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