BCOR modulates transcriptional activity of a subset of glucocorticoid receptor target genes involved in cell growth and mobility
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ABSTRACT:
PROVIDER: PRJNA684509 | ENA |
REPOSITORIES: ENA
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Project description:The effect of BCL6 corepressor (BCOR) on glucocorticoid signaling and was analyzed in HEK293-based cell lines using ChIP-seq and RNA-seq.
2021-04-15 | GSE163022 | GEO
Project description:Among acute myeloid leukemias (AML) with normal karyotype (CN-AML), NPM1 and CEBPA mutations define WHO provisional entities accounting for ~60% of cases, but the remaining ~40% remains poorly characterized. By whole exome-sequencing (WES) of one CN-AML patient lacking mutations in NPM1, CEBPA, FLT3, MLL-PTD and IDH1, we newly identified a clonal somatic mutation in BCOR (BCL6 co-repressor), a gene located in chromosome X. Further analyses showed that BCOR mutations occurred in 11/262 (4.2%) CN-AML cases and represented a substantial fraction (14/82, 17.1%) of CN-AML patients showing the same genetic background as the index patient subjected to WES. BCOR somatic mutations were: i) disruptive events similar to germline BCOR mutations causing the oculo-cranio-facial-dental (OCFD) genetic syndrome; ii) associated with markedly decreased BCOR mRNA levels, absence of full-length BCOR and absent or low expression of a truncated BCOR protein; iii) almost mutually exclusive with NPM1 mutations and frequently associated with DNMT3A and RUNX1 mutations, pointing to a cooperation between these events. Finally, BCOR mutations correlated with poor outcome among a cohort of 160 CN-AML patients (28% versus 66% overall survival at 2 yrs, P=0.024). Our results implicate for the first time BCOR in the pathogenesis of CN-AML without NPM1 mutations. AML samples with normal karyotype were studied. Molecular analyses were performed for BCOR mutations. 12 BCOR wild-type cases and 12 BCOR mutated cases were hybridized to gene expression micro-arrays.
2011-12-16 | E-GEOD-30442 | biostudies-arrayexpress
Project description:BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1) complex. Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukaemia (AML). However the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine cell models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with reduced protein levels of RING1B, a ubiquitin ligase subunit of PRC1 family complexes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with proliferation and myeloid differentiation and decreased stem cell quiescence. Further, we used a MLL-AF9 murine model of AML and found that loss of Bcor increased serial replating efficiency, enhanced MLL-AF9 in blocking cell differentiation, and increased expression of Evi1 which is associated with leukemic transformation. Our results strongly suggest that BCOR plays an indispensable role in maintaining hematopoietic stem cell (HSC) quiescence by inhibiting myeloid stem cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes. Normal karyotype AML primary cells with either wild type BCOR (6 cases) or destructive mutated BCOR (6 cases) were collected and subjected to RNA expression microarray study
2015-12-31 | E-GEOD-69565 | biostudies-arrayexpress
Project description:BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1) complex. Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukaemia (AML). However the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine cell models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with reduced protein levels of RING1B, a ubiquitin ligase subunit of PRC1 family complexes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with proliferation and myeloid differentiation and decreased stem cell quiescence. Further, we used a MLL-AF9 murine model of AML and found that loss of Bcor increased serial replating efficiency, enhanced MLL-AF9 in blocking cell differentiation, and increased expression of Evi1 which is associated with leukemic transformation. Our results strongly suggest that BCOR plays an indispensable role in maintaining hematopoietic stem cell (HSC) quiescence by inhibiting myeloid stem cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes. We took advantage of a mouse conditional Bcor allele which has exons 9 and 10 been flanked by LoxP sites to allow their removal via expression of Cre recombinase. Excision of these exons results in a frame shift and a premature stop codon causing nonsense mediated decay and/or carboxy-terminal deletion of the BCOR protein. CD34+ cells were sorted from control or Bcor mutant cells cultured under myeloid stem/progenitor conditions (IL3, 6 and SCF). We used microarrays to detail the global programme of gene expression in Control and Bcor mutant CD34+ cells.
2015-12-31 | E-GEOD-69620 | biostudies-arrayexpress
Project description:Genomewide DNA methylation array profiling of 37 BCOR altered tumors and 37 non-BCOR altered tumors to study the rare tumor entity of EP300::BCOR fusion in central nervous system. The raw methylation idat files and processed beta values were provided here.
2022-10-09 | GSE211156 | GEO
Project description:BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1) complex. Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukaemia (AML). However the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine cell models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with reduced protein levels of RING1B, a ubiquitin ligase subunit of PRC1 family complexes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with proliferation and myeloid differentiation and decreased stem cell quiescence. Further, we used a MLL-AF9 murine model of AML and found that loss of Bcor increased serial replating efficiency, enhanced MLL-AF9 in blocking cell differentiation, and increased expression of Evi1 which is associated with leukemic transformation. Our results strongly suggest that BCOR plays an indispensable role in maintaining hematopoietic stem cell (HSC) quiescence by inhibiting myeloid stem cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes.
2015-12-31 | GSE69620 | GEO
Project description:BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1) complex. Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukaemia (AML). However the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine cell models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with reduced protein levels of RING1B, a ubiquitin ligase subunit of PRC1 family complexes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with proliferation and myeloid differentiation and decreased stem cell quiescence. Further, we used a MLL-AF9 murine model of AML and found that loss of Bcor increased serial replating efficiency, enhanced MLL-AF9 in blocking cell differentiation, and increased expression of Evi1 which is associated with leukemic transformation. Our results strongly suggest that BCOR plays an indispensable role in maintaining hematopoietic stem cell (HSC) quiescence by inhibiting myeloid stem cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes.
2015-12-31 | GSE69565 | GEO
Project description:Among acute myeloid leukemias (AML) with normal karyotype (CN-AML), NPM1 and CEBPA mutations define WHO provisional entities accounting for ~60% of cases, but the remaining ~40% remains poorly characterized. By whole exome-sequencing (WES) of one CN-AML patient lacking mutations in NPM1, CEBPA, FLT3, MLL-PTD and IDH1, we newly identified a clonal somatic mutation in BCOR (BCL6 co-repressor), a gene located in chromosome X. Further analyses showed that BCOR mutations occurred in 11/262 (4.2%) CN-AML cases and represented a substantial fraction (14/82, 17.1%) of CN-AML patients showing the same genetic background as the index patient subjected to WES. BCOR somatic mutations were: i) disruptive events similar to germline BCOR mutations causing the oculo-cranio-facial-dental (OCFD) genetic syndrome; ii) associated with markedly decreased BCOR mRNA levels, absence of full-length BCOR and absent or low expression of a truncated BCOR protein; iii) almost mutually exclusive with NPM1 mutations and frequently associated with DNMT3A and RUNX1 mutations, pointing to a cooperation between these events. Finally, BCOR mutations correlated with poor outcome among a cohort of 160 CN-AML patients (28% versus 66% overall survival at 2 yrs, P=0.024). Our results implicate for the first time BCOR in the pathogenesis of CN-AML without NPM1 mutations.
2011-12-16 | GSE30442 | GEO
Project description:The identification of subtype-specific translocations has revolutionized diagnostics of sarcoma and provided new insight into oncogenesis. We used RNA-Seq to investigate samples diagnosed as small round cell tumors of bone, possibly Ewing sarcoma, but lacking the canonical EWSR1-ETS translocation. A new fusion was observed between the BCL6 co-repressor (BCOR) and the testis specific cyclin B3 (CCNB3) genes on chromosome X. RNA-Seq results were confirmed by RT-PCR and cloning the tumor-specific genomic translocation breakpoints. 24 BCOR-CCNB3-positive tumors were identified among a series of 594 sarcomas. Gene profiling experiments indicate that BCOR-CCNB3-positive cases are biologically distinct from other sarcomas, particularly EwingM-bM-^@M-^Ys sarcoma. Finally, we show that CCNB3 immunohistochemistry is a powerful diagnostic marker for this group of sarcoma and that over-expression of BCOR-CCNB3 or of a truncated CCNB3 activates S-phase in NIH3T3 cells. Thus the intrachromosomal X fusion described here represents a new subtype of bone sarcoma caused by a novel gene fusion mechanism. Comparison of expression profiles of 10 BCOR-CCNB3 samples (plus 4 EWS-FLI1 Ewing sarcomas samples as control) with publicly available profiles of other tumor types.
2012-03-03 | E-GEOD-34800 | biostudies-arrayexpress
Project description:Investigation of the epigenetic profile induced by Bcor loss
2019-02-07 | GSE126173 | GEO