Arrayed gene expression analysis of the SETD1A depleted cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE71498 | GEO | 2017/07/18
SECONDARY ACCESSION(S): PRJNA291400
REPOSITORIES: GEO
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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:SETD1A is a histone H3K4 methyltransferase and function as a coactivator for nuclear receptors (NRs) and other transcription factors. We performed genome-wide gene expression analysis in non-specific siRNA transfected or SETD1A knockdown MCF-7 cells to investigate global gene expression changes induced by SETD1A knockdown.
2018-10-24 | GSE101860 | 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 | 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: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
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.
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Project description:The modulation of chromatin structure is a key step in transcription regulation in eukaryotic cells. Mammalian erythropoiesis is accompanied by dynamic alterations in chromatin structure and gene expression, but the epigenetic regulators that modulate and coordinate these changes are largely unknown. USF, Setd1a and NURF complexes interact to regulate chromatin architecture in erythropoiesis, but the basis for this regulation is unknown. We studied this process using both murine and human models of erythropoiesis. In human primary erythroid cells, H3K4me3, USF1/2, and BPTF, a component of the NURF complex, were significantly co-enriched at more than 50% of transcription start sites (TSSs) of erythroid genes, associated with repositioning of promoter- or enhancer-associated nucleosomes. Depletion of Setd1a, an H3K4 trimethylase, led to a reduction of promoter-associated H3K4 methylation, inhibition of gene transcription and blockade of erythroid differentiation. This was associated with alterations in NURF complex-mediated nucleosome repositioning at erythroid gene promoters and chromatin accessibility. Setd1a deficiency caused decreased associations between the LCR and the -major globin promoter as well as reduced expression of the adult β-globin gene. In vivo, mice deficient for Setd1a in the erythroid compartment resulted in reduced Ter119/CD71 positive bone marrow erythroblasts, peripheral blood RBCs, and hemoglobin levels. These data indicate that Setd1a and NURF complexes coordinately regulate erythroid promoter chromatin dynamics during erythroid differentiation.
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Project description:Affinity Purification and Mass Spectrometry (AP-MS) using the phosphorylated RNAPII C-terminal domain (CTD) identified the capping enzyme and the H3K4 methyltransferase complex SETD1A/B. Subsequent inhibition of CDK7 revealed displaced H3K4me3 marks at the 3'-end of genes.
2017-05-10 | MSV000081069 | MassIVE
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:Quiescence, a hallmark of adult neural stem cells (NSCs), is required for maintaining the NSC pool to support life-long continuous neurogenesis in the adult dentate gyrus (DG). Whether epigenetic mechanisms can maintain NSC quiescence over long term in the adult brain is not well-understood. Here we showed that adult mice with haploinsufficiency of Setd1a, a schizophrenia risk gene encoding a histone H3K4 methyltransferase, exhibited substantially enlarged DG with increased number of dentate granule cells. Deletion of Setd1a specifically in quiescent NSCs in the adult DG promoted their activation and neurogenesis, which was countered by inhibition of histone demethylase LSD1. Mechanistically, RNA sequencing and CUT & RUN analyses of cultured quiescent adult NSCs revealed Setd1a deletion-induced transcriptional changes and Setd1a targets, among which down-regulation of Bhlhe40 promoted quiescent NSC activation in the adult DG. Together, our study revealed a Setd1a-dependent epigenetic mechanism that sustains NSC quiescence in the adult DG.
2024-03-31 | GSE250276 | GEO