ArticleCell death and differentiation2013
Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis resistance in leukaemia.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Effects of BCL-2 and MCL-1 Inhibition on Apoptotic and Transcriptional Profiles in Acute Myeloid Leukemia.Medicina (Kaunas, Lithuania) · 2026Article
- Therapeutic targeting SPI1 in combination with erastin promotes ferroptosis in ccRCC.Communications biology · 2025Article
- Intracellular checkpoints for NK cell cancer immunotherapy.Frontiers of medicine · 2024Review
- HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependent gene repression in murine erythroleukaemia.Nucleic acids research · 2022Article
- Hexokinase 3 enhances myeloid cell survival via non-glycolytic functions.Cell death & disease · 2022Article
- Allele-specific DNA methylation maps in monozygotic twins discordant for psychiatric disorders reveal that disease-associated switching at the EIPR1 regulatory loci modulates neural function.Molecular psychiatry · 2021Article
- The Pivotal Immunomodulatory and Anti-Inflammatory Effect of Histone-Lysine N-Methyltransferase in the Glioma Microenvironment: Its Biomarker and Therapy Potentials.Analytical cellular pathology (Amsterdam) · 2021Review
- Resistance to anti-microtubule drug-induced cell death is determined by regulation of BimEL expression.Oncogene · 2019Article
- Senescence is a Spi1-induced anti-proliferative mechanism in primary hematopoietic cells.Haematologica · 2017Article
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- The Spi1/PU.1 transcription factor accelerates replication fork progression by increasing PP1 phosphatase in leukemia.Oncotarget · 2017Article
- PU.1 supports TRAIL-induced cell death by inhibiting NF-κB-mediated cell survival and inducing DR5 expression.Cell death and differentiation · 2017Article
- Significance of Inactivated Genes in Leukemia: Pathogenesis and Prognosis.Cell journal · 2017Review
- Transcription factors, coregulators, and epigenetic marks are linearly correlated and highly redundant.PloS one · 2017Article
- NT1721, a novel epidithiodiketopiperazine, exhibits potent in vitro and in vivo efficacy against acute myeloid leukemia.Oncotarget · 2016Article
- EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling.Oncotarget · 2016Article
- Low BIK outside-inside-out interactive inflammation immune-induced transcription-dependent apoptosis through FUT3-PMM2-SQSTM1-SFN-ZNF384.Immunologic research · 2016Article
- Regulation of Bim in Health and Disease.Oncotarget · 2015Review
- ARE/SUZ12 dual specifically-regulated adenoviral TK/GCV system for CML blast crisis cells.Journal of experimental & clinical cancer research : CR · 2015Article
- Trichostatin A specifically improves the aberrant expression of transcription factor genes in embryos produced by somatic cell nuclear transfer.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deregulation of transcriptional networks contributes to haematopoietic malignancies. The transcription factor Spi-1/PU.1 is a master regulator of haematopoiesis and its alteration leads to leukaemia. Spi-1 overexpression inhibits differentiation and promotes resistance to apoptosis in erythroleukaemia. Here, we show that Spi-1 inhibits mitochondrial apoptosis in vitro and in vivo through the transcriptional repression of Bim, a proapoptotic factor. BIM interacts with MCL-1 that behaves as a major player in the survival of the preleukaemic cells. The repression of BIM expression reduces the amount of BIM-MCL-1 complexes, thus increasing the fraction of potentially active antiapoptotic MCL-1. We then demonstrate that Spi-1 represses Bim transcription by binding to the Bim promoter and by promoting the trimethylation of histone 3 on lysine 27 (H3K27me3, a repressive histone mark) on the Bim promoter. The PRC2 repressive complex of Polycomb is directly responsible for the deposit of H3K27me3 mark at the Bim promoter. SUZ12 and the histone methyltransferase EZH2, two PRC2 subunits bind to the Bim promoter at the same location than H3K27me3, distinct of the Spi-1 DNA binding site. As Spi-1 interacts with SUZ12 and EZH2, these results indicate that Spi-1 modulates the activity of PRC2 without directly recruiting the complex to the site of its activity on the chromatin. Our results identify a new mechanism whereby Spi-1 represses transcription and provide mechanistic insights on the antiapoptotic function of a transcription factor mediated by the epigenetic control of gene expression.
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