The CXXC5-CRL4B-NuRD Repressor Complex Promotes Breast Carcinogenesis by Regulating the TSC1/mTOR pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA844613 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19521716_1.fastq.gz | Fastqsanger.gz | |||
| SRR19521716_2.fastq.gz | Fastqsanger.gz | |||
| SRR19521717_1.fastq.gz | Fastqsanger.gz | |||
| SRR19521717_2.fastq.gz | Fastqsanger.gz | |||
| SRR19521718_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for CXXC5,CUL4B as well as MTA1 in MCF-7 cells.The pathophysiological function of the CXXC family-member CXXC5 remains to be explored. Here we report that CXXC5 is physically associated with the CRL4B complex and the NuRD complex. Genome-wide investigation of transcriptional targets revealed that the CXXC5/CRL4B/NuRD complex represses a panel of genes including TSC1 that are critically involved in cell growth and the regulation of the mTOR pathway, leading to activation of PD-L1. Intriguingly, CXXC5 expression was increased after stimulation with vitamin B2, whereas vitamin D treatment was accompanied by decreased expression of CXXC5. We demonstrated that the CXXC5-CRL4B-NuRD complex promotes cancer cell proliferation. Elevation of CXXC5, CUL4B, and MTA1 expression during cancer progression corresponded to diminished TSC1 expression, and high levels of CXXC5, CUL4B, and MTA1 strongly correlated with higher histological grades and poor prognosis. We further identified that CXXC5 is bimodally regulated by different kinds of vitamins. Our study revealed that CXXC5-mediated TSC1 suppression activates the mTOR pathway, reduces autophagic cell death, induces PD-L1-mediated immune suppression and results in tumor development, providing a possible mechanistic insight into the pathophysiological function of CXXC5.
2022-12-12 | GSE205362 | GEO
Project description:To study the effect of knockdown of Cxxc5 on stem/progenitor cells, we used retrovirus to knockdown Cxxc5 expression in the LSK cells. We used this as a surrogate to study the function of Cxxc5 in mouse/stem progenitor cells.
2020-02-14 | GSE145246 | GEO
Project description:Mammalian genomes encode a family of 12 proteins that contain a CXXC zinc finger domain. These domains are known to bind to unmethylated DNA sequences rich in CpG dinucleotides. Most members of this family are large multi-domain proteins that function in the control of DNA methylation and histone methylation patterns. CXXC5 is a smaller member of the family, along with its closest homologue CXXC4. These two proteins lack known catalytic domains. Here we have characterized CXXC5 in mouse embryonic stem (ES) cells. We show that CXXC5 is a nuclear protein that interacts with 5-methylcytosine oxidases (TET proteins). Removal of CXXC5 from ES cells leads to very few changes in gene expression. CXXC5 extensively colocalizes with TET1 and TET2 at CpG islands. CXXC5 inactivation leads to a substantial reduction of DNA methylation levels that affects all genomic compartments including genic and intergenic regions and CpG island shores. No hypermethylation of CpG islands was observed. We propose a model in which CXXC5 serves as an anchor for TET proteins at CpG islands. In the absence of CXXC5, the 5-methylcytosine oxidases become dislodged from CpG islands and are enabled to induce genome-scale DNA demethylation. Thus, CXXC5 serves as a stabilizer of DNA methylation patterns.
2024-06-04 | GSE268884 | GEO
Project description:Mammalian genomes encode a family of 12 proteins that contain a CXXC zinc finger domain. These domains are known to bind to unmethylated DNA sequences rich in CpG dinucleotides. Most members of this family are large multi-domain proteins that function in the control of DNA methylation and histone methylation patterns. CXXC5 is a smaller member of the family, along with its closest homologue CXXC4. These two proteins lack known catalytic domains. Here we have characterized CXXC5 in mouse embryonic stem (ES) cells. We show that CXXC5 is a nuclear protein that interacts with 5-methylcytosine oxidases (TET proteins). Removal of CXXC5 from ES cells leads to very few changes in gene expression. CXXC5 extensively colocalizes with TET1 and TET2 at CpG islands. CXXC5 inactivation leads to a substantial reduction of DNA methylation levels that affects all genomic compartments including genic and intergenic regions and CpG island shores. No hypermethylation of CpG islands was observed. We propose a model in which CXXC5 serves as an anchor for TET proteins at CpG islands. In the absence of CXXC5, the 5-methylcytosine oxidases become dislodged from CpG islands and are enabled to induce genome-scale DNA demethylation. Thus, CXXC5 serves as a stabilizer of DNA methylation patterns.
2024-06-04 | GSE268885 | GEO
Project description:Mammalian genomes encode a family of 12 proteins that contain a CXXC zinc finger domain. These domains are known to bind to unmethylated DNA sequences rich in CpG dinucleotides. Most members of this family are large multi-domain proteins that function in the control of DNA methylation and histone methylation patterns. CXXC5 is a smaller member of the family, along with its closest homologue CXXC4. These two proteins lack known catalytic domains. Here we have characterized CXXC5 in mouse embryonic stem (ES) cells. We show that CXXC5 is a nuclear protein that interacts with 5-methylcytosine oxidases (TET proteins). Removal of CXXC5 from ES cells leads to very few changes in gene expression. CXXC5 extensively colocalizes with TET1 and TET2 at CpG islands. CXXC5 inactivation leads to a substantial reduction of DNA methylation levels that affects all genomic compartments including genic and intergenic regions and CpG island shores. No hypermethylation of CpG islands was observed. We propose a model in which CXXC5 serves as an anchor for TET proteins at CpG islands. In the absence of CXXC5, the 5-methylcytosine oxidases become dislodged from CpG islands and are enabled to induce genome-scale DNA demethylation. Thus, CXXC5 serves as a stabilizer of DNA methylation patterns.
2024-06-04 | GSE268886 | GEO
Project description:CXXC5 inhibits the canonical Wnt signaling pathway Impact of CXXC5 on Wnt stimulated gene expression in K562 cells
2015-03-20 | GSE67060 | GEO
Project description:We have employed whole genome microarray expression profiling as a discovery platform to identify genes regulated by CXXC5 in pDCs. pDCs (CD11c+B220+CD11b-) were differentitated from wild-type and CXXC5-deficient bone marrows by FLT3L for 6 days and sorted by FACS. Expression of five genes (Irf7,Ccl1,Smtn,Dppa2,Ifnab) from this signature was quantified in the same RNA samples by real-time PCR.
2017-04-07 | GSE79643 | GEO
Project description:The aim of this work was to elucidate the role of the transcription factor CXXC5 in glioblastoma and study its involvement in the regulation of TGFβ and BMP target genes in this context. To this end we used the patient derived glioblastoma stem cells U3034MG that were either transfected with siRNA targeting CXXC5 or with a non-targeting pool (as control) followed by stimulation with either 5ng/ml TGFβ or 30ng/ml BMP7 for 24 h. Then we analysed how silencing CXXC5 affects the expression of TGFβ and/or BMP7 target genes using Ion torrent AmpliseqTM.
2021-05-01 | E-MTAB-9813 | biostudies-arrayexpress
Project description:The evolutionary conserved histone variant H2A.Z plays a crucial role in various DNA-based processes but the underlying mechanisms are not completely understood. Recently, we identified the zinc finger (ZNF) protein ZNF512B as an H2A.Z-, HMG20A- and PWWP2A-associated protein. Here, we report ZNF512B as a novel nucleosome remodeling and deacetylase (NuRD) complex binding protein. We discovered a conserved amino acid sequence within ZNF512B that resembles a NuRD-interaction domain (NIM) previously identified in FOG-1. By solving the crystal structure of this domain directly bound to the NuRD component RBBP4 and by applying several biochemical assays we demonstrate that this novel internal NIM sequence is both necessary and sufficient for high-affinity NuRD binding. Transcriptome analyses and reporter assays identify ZNF512B as regulator (repressor) of gene expression, in both NuRD-dependent and -independent modes. Surprisingly, high levels of ZNF512B expression lead to concomitant nuclear protein and chromatin aggregation foci that form independent of the interaction with the NuRD complex but depend on ZNF512B’s zinc fingers. Our study has implications for diseases in which ZNF512B’s expression is deregulated, such as cancer and neurodegenerative diseases and reveal the existence of more proteins as potential NuRD interactors.
2024-10-29 | GSE236639 | GEO
Project description:The evolutionary conserved histone variant H2A.Z plays a crucial role in various DNA-based processes but the underlying mechanisms are not completely understood. Recently, we identified the zinc finger (ZNF) protein ZNF512B as an H2A.Z-, HMG20A- and PWWP2A-associated protein. Here, we report ZNF512B as a novel nucleosome remodeling and deacetylase (NuRD) complex binding protein. We discovered a conserved amino acid sequence within ZNF512B that resembles a NuRD-interaction domain (NIM) previously identified in FOG-1. By solving the crystal structure of this domain directly bound to the NuRD component RBBP4 and by applying several biochemical assays we demonstrate that this novel internal NIM sequence is both necessary and sufficient for high-affinity NuRD binding. Transcriptome analyses and reporter assays identify ZNF512B as regulator (repressor) of gene expression, in both NuRD-dependent and -independent modes. Surprisingly, high levels of ZNF512B expression lead to concomitant nuclear protein and chromatin aggregation foci that form independent of the interaction with the NuRD complex but depend on ZNF512B’s zinc fingers. Our study has implications for diseases in which ZNF512B’s expression is deregulated, such as cancer and neurodegenerative diseases and reveal the existence of more proteins as potential NuRD interactors.
2024-10-30 | PXD043366 | Pride