Modulation of gene expression by ZNF143, THAP11 and NOTCH1 via overlapping binding sites in mammalian cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA170436 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR520390.fastq.gz | Fastqsanger.gz | |||
| SRR520391.fastq.gz | Fastqsanger.gz | |||
| SRR520392.fastq.gz | Fastqsanger.gz | |||
| SRR520393.fastq.gz | Fastqsanger.gz | |||
| SRR520394.fastq.gz | Fastqsanger.gz |
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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:ZNF143 is a zinc-finger protein involved in the transcriptional regulation of both coding and non-coding genes from polymerase II and III promoters. Our study deciphers the genome-wide regulatory role of ZNF143 in relation with the two previously unrelated transcription factors Notch1/ICN1 and thanatos-associated protein 11 (THAP11) in several human and murine cells. We show that two distinct motifs, SBS1 and SBS2, are associated to ZNF143-binding events in promoters of >3000 genes. Without co-occupation, these sites are also bound by Notch1/ICN1 in T-lymphoblastic leukaemia cells as well as by THAP11, a factor involved in self-renewal of embryonic stem cells. We present evidence that ICN1 binding overlaps with ZNF143 binding events at the SBS1 and SBS2 motifs, whereas the overlap occurs only at SBS2 for THAP11. We demonstrate that the three factors modulate expression of common target genes through the mutually exclusive occupation of overlapping binding sites. The model we propose predicts that the binding competition between the three factors controls biological processes such as rapid cell growth of both neoplastic and stem cells. Overall, our study establishes a novel relationship between ZNF143, THAP11 and ICN1 and reveals important insights into ZNF143-mediated gene regulation.
| 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:The THAP11 and ZNF143 transcription factors recognize overlapping DNA sequences and are reported to exhibit signs of both competitive and cooperative binding. HCFC1 serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators. The exact mechanism of how DNA sequences guide the recruitment of the THAP11/ZNF143/HCFC1 complex to chromatin is still controversial. In this study, we use chromosomally integrated synthetic constructs and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated approaches in intact cells to elucidate the role of the DNA sequence in the recruitment of this complex and to establish its biological relevance. We show that the ACTACA submotif, shared by both THAP11 and ZNF143, directs the recruitment of THAP11 and HCFC1 to ZNF143-occupied loci. Importantly, its position, spacing, and orientation relative to the ZNF143 core motif are critical for this action. CRISPR-Cas9-mediated alterations of the ACTACA submotif at endogenous promoters recapitulated results obtained with synthetic constructs and resulted in altered gene transcription and histone modifications at targeted promoters. Our in vivo approaches provide strong evidence for the molecular role of the ACTACA submotif in THAP11, ZNF143, and HCFC1 cooperative recruitment to chromatin and its biological role in target gene expression.
| S-EPMC4648815 | biostudies-literature
Project description:Gene expression is orchestrated by transcription factors (TFs), which bind to DNA in a sequence-specific manner, and by spatial genome structure, which constrains and shapes TF activity. Zinc finger protein 143 (ZNF143/ZFP143) is a TF that has been implicated in both gene activation and 3D genome organisation. We have generated an acute ZNF143/ZFP143 depletion system to study its direct consequences on chromatin looping and gene transcription. The effects of ZNF143/ZFP143 depletion are inconsistent with it being a looping factor, which we further confirmed by systematic analysis of previous studies. However, degradation of ZNF143/ZFP143 led to the down-regulation of hundreds of its targets, which were found to be enriched in nuclear-encoded mitochondrial genes. By studying the consequences of ZNF143/ZFP143 loss in monoculture and in an in vitro embryonic development model, we establish ZNF143/ZFP143 as a conserved transcriptional regulator of cell proliferation and differentiation by modulating mitochondrial functions.
2024-03-08 | PXD049480 | Pride
Project description:The transcription factor ZNF143 contains seven tandem zinc fingers and is involved in 3D genome construction; however, the mechanism by which ZNF143 functions in chromatin looping remains unclear. Here, we show that ZNF143 directionally recognizes diverse genomic sites and is required for chromatin looping between these sites. In addition, ZNF143 is located between CTCF and cohesin at numerous CTCF sites and ZNF143 removal narrows the space between CTCF and cohesin. Moreover, genetic deletion of ZNF143, in conjunction with acute CTCF depletion, revealed that ZNF143 and CTCF collaborate to regulate higher-order genome organization. Thus, ZNF143 is recruited by CTCF to the CTCF sites to regulate TAD formation and genome compartmentalization whereas directional recognition of DNA motifs directly by ZNF143 itself regulates promoter activity via chromatin looping.
2023-11-07 | GSE236635 | GEO
Project description:The transcription factor ZNF143 contains seven tandem zinc fingers and is involved in 3D genome construction; however, the mechanism by which ZNF143 functions in chromatin looping remains unclear. Here, we show that ZNF143 directionally recognizes diverse genomic sites and is required for chromatin looping between these sites. In addition, ZNF143 is located between CTCF and cohesin at numerous CTCF sites and ZNF143 removal narrows the space between CTCF and cohesin. Moreover, genetic deletion of ZNF143, in conjunction with acute CTCF depletion, revealed that ZNF143 and CTCF collaborate to regulate higher-order genome organization. Thus, ZNF143 is recruited by CTCF to the CTCF sites to regulate TAD formation and genome compartmentalization whereas directional recognition of DNA motifs directly by ZNF143 itself regulates promoter activity via chromatin looping.
2023-11-07 | GSE236631 | GEO