Modulation of gene expression by ZNF143, THAP11 and NOTCH1 via overlapping binding sites in mammalian cells
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PROVIDER: PRJNA170436 | ENA |
REPOSITORIES: ENA
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Project description:In this study we investigated the genome wide DNA binding profile of ZNF143 and ICN1 in human and murine cells. We also analyzed the expression profile in human cells after overexpression or knockdown of ZNF143. To identify ZNF143 targets we performed ChIP-seq on 4 human cells lines and 3 murine cell types. We also identified, by ChIP-seq, ICN1 binding sites in HPB-ALL cells. To identify directly regulated genes by ZNF143, we analyzed, by RNA-seq, the expression profile after knockdown and overexpression of the transcription factor.
2013-02-13 | E-GEOD-39263 | biostudies-arrayexpress
Project description:In this study we investigated the genome wide DNA binding profile of ZNF143 and ICN1 in human and murine cells. We also analyzed the expression profile in human cells after overexpression or knockdown of ZNF143.
2013-02-13 | GSE39263 | GEO
Project description: Not available
| S-EPMC3627581 | biostudies-literature
Project description:Notch1 regulates gene expression by associating with the DNA-binding factor RBPJ and is oncogenic in murine and human T cell progenitors. Using ChIP-Seq, we find that in human and murine T-LL genomes Notch1 binds preferentially to promoters, to RBPJ binding sites, and near imputed ZNF143, Ets and Runx sites. ChIP-Seq confirmed that ZNF143 binds to ~40% of Notch1 sites. Notch1/ZNF143 sites are characterized by high Notch1 and ZNF143 signals, frequent co-binding of RBPJ (generally through sites embedded within ZNF143 motifs), strong promoter bias, and relatively low mean levels of activating chromatin marks. RBPJ and ZNF143 binding to DNA is mutually exclusive in vitro, suggesting RBPJ/Notch1 and ZNF143 complexes exchange on these sites in cells. K-means clustering of Notch1 binding sites and associated motifs identified conserved Notch1-Runx, Notch1-Ets, Notch1-RBPJ, Notch1-ZNF143, and Notch1-ZNF143-Ets clusters with different genomic distributions and levels of chromatin marks. Although Notch1 binds mainly to gene promoters, ~75% of direct target genes lack promoter binding and are presumably regulated by enhancers, which were identified near MYC, DTX1, IGF1R, IL7R and the GIMAP cluster. Human and murine T-LL genomes also have many sites that bind only RBPJ. Murine RBPJ M-CM-"M-BM-^@M-BM-^\onlyM-CM-"M-BM-^@M-BM-^] sites are highly enriched for imputed REST sites, whereas human RPBJ M-CM-"M-BM-^@M-BM-^\onlyM-CM-"M-BM-^@M-BM-^] sites lack REST motifs and are more highly enriched for imputed CREB sites. Thus, there is a conserved network of cis-regulatory factors that interacts with Notch1 to regulate gene expression in T-LL cells, as well as novel classes of divergent RBPJ M-CM-"M-BM-^@M-BM-^\onlyM-CM-"M-BM-^@M-BM-^] sites that also likely regulate transcription. Notch1, RBPJ, histone methylation ChIP-seq in human and mouse T-LL cell lines
2011-07-06 | E-GEOD-29600 | biostudies-arrayexpress
Project description:Notch1 regulates gene expression by associating with the DNA-binding factor RBPJ and is oncogenic in murine and human T cell progenitors. Using ChIP-Seq, we find that in human and murine T-LL genomes Notch1 binds preferentially to promoters, to RBPJ binding sites, and near imputed ZNF143, Ets and Runx sites. ChIP-Seq confirmed that ZNF143 binds to ~40% of Notch1 sites. Notch1/ZNF143 sites are characterized by high Notch1 and ZNF143 signals, frequent co-binding of RBPJ (generally through sites embedded within ZNF143 motifs), strong promoter bias, and relatively low mean levels of activating chromatin marks. RBPJ and ZNF143 binding to DNA is mutually exclusive in vitro, suggesting RBPJ/Notch1 and ZNF143 complexes exchange on these sites in cells. K-means clustering of Notch1 binding sites and associated motifs identified conserved Notch1-Runx, Notch1-Ets, Notch1-RBPJ, Notch1-ZNF143, and Notch1-ZNF143-Ets clusters with different genomic distributions and levels of chromatin marks. Although Notch1 binds mainly to gene promoters, ~75% of direct target genes lack promoter binding and are presumably regulated by enhancers, which were identified near MYC, DTX1, IGF1R, IL7R and the GIMAP cluster. Human and murine T-LL genomes also have many sites that bind only RBPJ. Murine RBPJ âonlyâ sites are highly enriched for imputed REST sites, whereas human RPBJ âonlyâ sites lack REST motifs and are more highly enriched for imputed CREB sites. Thus, there is a conserved network of cis-regulatory factors that interacts with Notch1 to regulate gene expression in T-LL cells, as well as novel classes of divergent RBPJ âonlyâ sites that also likely regulate transcription.
2011-07-06 | GSE29600 | GEO
Project description:Notch1 signaling is absolutely essential for steady-state thymic lymphopoiesis, but the role of other Notch receptors, and their potential overlap with the function of Notch1, remains unclear. Here we show that like Notch1, Notch3 is differentially expressed by progenitor thymocytes, peaking at the DN3 progenitor stage. Using mice carrying a gene-trapped allele, we show that thymic cellularity is slightly reduced in the absence of Notch3, although progression through the defined sequence of TCR-αβ development is normal, as are NKT and TCRγδ cell production. The absence of a profound effect from Notch3 deletion is not explained by residual function of the gene-trapped allele, since insertion mapping suggests that the targeted allele would not encode functional signaling domains. We also show that although Notch1 and Notch3 are co-expressed on some early intrathymic progenitors, the relatively mild phenotype seen after Notch3 deletion does not result from the compensatory function of Notch1, nor does Notch3 function explain the likewise mild phenotype seen after conditional (intrathymic) deletion of Notch1. Our studies indicate that Notch1 and Notch3 carry out non-overlapping functions during thymocyte differentiation, and that while Notch1 is absolutely required early in the lymphopoietic process, neither receptor is essential at later stages.
2011-08-03 | GSE30631 | GEO
Project description:RNA-seq of Ronin/Thap11 knockout and heterozygous control mouse ES cells to assess the role of Ronin
2022-01-31 | E-MTAB-10024 | biostudies-arrayexpress
Project description:Analysis of transcriptional regulation in human cells has implicated a large number of promoter-specific DNA-binding proteins that regulate transcription via diverse mechanisms. In some cases, these DNA-sequence-specific factors associate with intermediaries that orchestrate interactions with the chromatin-modifying enzymes. One such intermediary is HCF-1 (host-cell factor-1; HCFC1). HCF-1, first identified for its involvement in herpes-simplex virus transcription and subsequently shown to be an important cell-cycle regulator, has a poorly defined role in genome-wide transcriptional regulation. We show here, by chromatin immunoprecipitation followed by high-throughput sequence analysis (ChIP-seq), that HCF-1 is a major transcriptional start site associated factor, whose promoter association correlates positively with transcriptional activity. Thus, in HeLa cells HCF-1 is observed on 5400 generally active CpG-island promoters. Examination of the DNA sequences underlying the HCF-1-binding sites revealed three sequence motifs associated with the binding of (i) ZNF143 and Ronin/THAP11, (ii) GABP, and (iii) YY1 sequence-specific transcription factors. Subsequent ChIP-seq analysis of these four transcription factors revealed a large co-association of HCF-1 with these four transcription factors at approximately 90% of HCF-1-bound promoters. These studies suggest that a relatively small number of transcription factors -- some (ZNF143 and Ronin/THAP11) in novel combinations -- play a major role in HeLa-cell transcriptional regulation in association with HCF-1. This experiment includes the sequencing data of material obtained from chromatin immunoprecipitation using antibodies against HCFC1(antibodies against the C-subunit and the N-subunit), PolII(antibody against the RPB2 subunit), H3K36ME3 and H3K4Me3 histone modifications, ZNF143, THAP11, GABPalpha and YY1. It also includes control data of the Input material. All of them were done using HeLa cycling cells.
2012-07-31 | E-GEOD-31417 | biostudies-arrayexpress
Project description:Twelve human THAP proteins share the THAP domain, an evolutionary conserved zinc-finger DNA-binding domain. Studies of different THAP proteins have indicated roles in gene transcription, cell proliferation and development. We have analyzed this protein family, focusing on THAP7 and THAP11. We show that human THAP proteins possess differing homo- and heterodimer formation properties and interaction abilities with the transcriptional co-regulator HCF-1. HEK-293 cells lacking THAP7 were viable but proliferated more slowly. In contrast, HEK-293 cells were very sensitive to THAP11 alteration. Nevertheless, HEK-293 cells bearing a human THAP11 mutation identified in a patient suffering from cobalamin disorder (THAP11F80L) were viable although proliferated more slowly. Cobalamin disorder is an inborn vitamin deficiency characterized by neurodevelopmental abnormalities, most often due to biallelic mutations in the MMACHC gene, whose gene product MMACHC is a key enzyme in the cobalamin metabolic pathway. We show that THAP11F80L selectively affected promoter binding by THAP11, having more deleterious effects on a subset of THAP11 targets, and resulting in altered patterns of gene expression. In particular, THAP11F80L exhibited a strong effect on association with the MMACHC promoter and led to a decrease in MMACHC gene transcription, suggesting that the THAP11F80L mutation is directly responsible for the observed cobalamin disorder.
2019-12-20 | GSE138207 | GEO
Project description:Twelve human THAP proteins share the THAP domain, an evolutionary conserved zinc-finger DNA-binding domain. Studies of different THAP proteins have indicated roles in gene transcription, cell proliferation and development. We have analyzed this protein family, focusing on THAP7 and THAP11. We show that human THAP proteins possess differing homo- and heterodimer formation properties and interaction abilities with the transcriptional co-regulator HCF-1. HEK-293 cells lacking THAP7 were viable but proliferated more slowly. In contrast, HEK-293 cells were very sensitive to THAP11 alteration. Nevertheless, HEK-293 cells bearing a human THAP11 mutation identified in a patient suffering from cobalamin disorder (THAP11F80L) were viable although proliferated more slowly. Cobalamin disorder is an inborn vitamin deficiency characterized by neurodevelopmental abnormalities, most often due to biallelic mutations in the MMACHC gene, whose gene product MMACHC is a key enzyme in the cobalamin metabolic pathway. We show that THAP11F80L selectively affected promoter binding by THAP11, having more deleterious effects on a subset of THAP11 targets, and resulting in altered patterns of gene expression. In particular, THAP11F80L exhibited a strong effect on association with the MMACHC promoter and led to a decrease in MMACHC gene transcription, suggesting that the THAP11F80L mutation is directly responsible for the observed cobalamin disorder.
2019-12-20 | GSE138205 | GEO