ChIP-Seq based analysis of THAP1 binding in mouse ES cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE86911 | GEO | 2017/08/11
SECONDARY ACCESSION(S): PRJNA342945
REPOSITORIES: GEO
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Project description:We report the differences in mRNA profiles of WT mouse cells in comparison to both THAP1 -/- cells and cells in which a disease causing C54Y mutation was introduced.
2017-08-11 | GSE86947 | GEO
Project description:Goal of the experiment : Retroviral-mediated gene transfer of the THAP-zinc finger protein THAP1 inhibits endothelial cell proliferation through coordinated repression of critical cell cycle regulators and pRB-E2F target genes. Experimental design: To gain insight into the effects of THAP1 on endothelial cell growth regulatory pathways, we identified THAP1 target genes in primary human endothelial cells using oligonucleotide-based microarray technology. Human umbilical vein endothelial cells (HUVECs) were transduced with pMLV-MCS or pMLV-THAP1 retroviral expression vectors and, after 48h, cells were harvested for isolation of total RNA and preparation of Cy3- or Cy5-labeled cRNA probes, which were hybridized to DNA microarrays that contained 22 000 unique 60-nt oligonucleotide probes representing > 17 000 human genes. Independent microarray experiments were performed after one (#1xTHAP1) or two (#2xTHAP1) consecutive transductions using independent HUVEC primary cell cultures. Dye swap experiments were performed to eliminate the effect of dye bias, and for each gene probe, the data were subjected to statistical analysis to identify those probes for which a significant difference (p value < 0.01) in mean hybridization intensity was observed between HUVECs transduced with pMLV-MCS or pMLV-THAP1 retroviral expression vectors. Among the gene probes demonstrating a significant difference between the two conditions, we selected those whose expression varied in a similar manner in the two independent microarray experiments. . #2xTHAP1 experiment (Microarrays Code Bars 16011521022012 and 16011521022013): comparison of HUVEC-THAP1 and HUVEC-MCS after two consecutive retroviral transductions of HUVECs with pMLV-THAP1 or pMLV-MCS vectors (higher percentage of genes differentially expressed with p value < 0.01; higher folds) #1xTHAP1 experiment (Microarrays Code Bars 16011521025800 and 16011524025685): comparison of HUVEC-THAP1 and HUVEC-MCS after a single retroviral transduction of HUVECs with pMLV-THAP1 or pMLV-MCS vectors (lower percentage of genes differentially expressed with p value < 0.01; lower folds).
2006-09-11 | E-TABM-24 | biostudies-arrayexpress
Project description:We demonstrated previously that THAP1 plays a cell-autonomous role in regulating myelination during early postnatal CNS development (Yellajoshyula et al., Dev Cell, 42, 52-67, 2017). To begin to examine the mechanisms responsible for this role, we performed RNAseq at multiple time points on cultured control (Thap1+/+) and Thap1 null (derived from Thap1flx/-; Olig2-Cre+) OPC under differentiating conditions.
2021-04-24 | GSE161556 | GEO
Project description:THAP1 is a transcription factor and its mutations are responsible for DYT6 dystonia. However, how THAP1 mutations lead to these gene expression alterations and whether the gene expression changes are also reflected in the brain of THAP1 patients are still unclear. In this study we used epigenetic and transcriptomic approaches combined with multiple model systems to uncover the function of THAP1 and the potential pathogenesis of DYT6 dystonia. THAP1 mutations lead to dysregulation of genes mainly through regulation of SP1 family members, SP1 and SP4, in a cell type dependent manner.
2022-09-28 | GSE184959 | GEO
Project description:THAP1 is a transcription factor and its mutations are responsible for DYT6 dystonia. However, how THAP1 mutations lead to these gene expression alterations and whether the gene expression changes are also reflected in the brain of THAP1 patients are still unclear. In this study we used epigenetic and transcriptomic approaches combined with multiple model systems to uncover the function of THAP1 and the potential pathogenesis of DYT6 dystonia. THAP1 mutations lead to dysregulation of genes mainly through regulation of SP1 family members, SP1 and SP4, in a cell type dependent manner.
2022-09-28 | GSE184958 | GEO
Project description:THAP1 is a transcription factor and its mutations are responsible for DYT6 dystonia. However, how THAP1 mutations lead to these gene expression alterations and whether the gene expression changes are also reflected in the brain of THAP1 patients are still unclear. In this study we used epigenetic and transcriptomic approaches combined with multiple model systems to uncover the function of THAP1 and the potential pathogenesis of DYT6 dystonia. THAP1 mutations lead to dysregulation of genes mainly through regulation of SP1 family members, SP1 and SP4, in a cell type dependent manner.
2022-09-28 | GSE184957 | GEO
Project description:Loss of function mutations in the transcription factor THAP1 cause DYT6 dystonia, a childhood-onset motor disorder. DYT6 subjects display abnormalities in the white matter regions of the brain. Here, we generated conditional THAP1 knockout mice and analyzed the gene expression profiles from motor regions of mice brains to identify a role for THAP1 in the control of myelination
2017-07-10 | GSE97372 | GEO
Project description:The Shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and REV7, shields double strand DNA breaks (DSBs) from nucleolytic resection. The end-protecting activity of Shieldin promotes productive non-homologous end joining (NHEJ) in G1 but can threaten genome integrity during S-phase by blocking homologous recombination (HR). Curiously, the penultimate Shieldin component, SHLD1 is one of the least abundant mammalian proteins. Here, we report that the transcription factors THAP1, YY1 and HCF1 bind directly to the SHLD1 promoter, where they cooperatively maintain the low basal expression of SHLD1. Functionally, this transcriptional network ensures that SHLD1 protein levels are kept in check to enable a proper balance between end protection and end resection during physiological DSB repair. In the context of BRCA1 deficiency, loss of THAP1 dependent SHLD1 expression confers cross resistance to PARP inhibitor and cisplatin, and shorter progression free survival in ovarian cancer patients. In contrast, loss of THAP1 in BRCA2 deficient cells increases genome instability and correlates with improved responses to chemotherapy. Pathogenic THAP1 mutations are causatively linked to adult-onset torsion dystonia type 6 (DYT6) movement disorder, but the critical disease targets are unknown. We further demonstrate that murine models of Thap1-associated dystonia show reduced Shld1 expression concomitant with elevated levels of unresolved DNA damage in the brain. In summary, our study provides the first example of a transcriptional network that directly controls DSB repair choice and reveals a previously unsuspected link between DNA damage and dystonia.
2021-04-13 | GSE154726 | GEO
Project description:Analysis of wild type, PKm1 KI, 2TS22c and, ZHBTc4 ES cell lines and Embryoid Body from wild type ES cells.
2015-06-01 | GSE57610 | GEO
Project description:The Shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and REV7, shields double strand DNA breaks (DSBs) from nucleolytic resection. The end-protecting activity of Shieldin promotes productive non-homologous end joining (NHEJ) in G1 but can threaten genome integrity during S-phase by blocking homologous recombination (HR). Curiously, the penultimate Shieldin component, SHLD1 is one of the least abundant mammalian proteins. Here, we report that the transcription factors THAP1, YY1 and HCF1 bind directly to the SHLD1 promoter, where they cooperatively maintain the low basal expression of SHLD1. Functionally, this transcriptional network ensures that SHLD1 protein levels are kept in check to enable a proper balance between end protection and end resection during physiological DSB repair. In the context of BRCA1 deficiency, loss of THAP1 dependent SHLD1 expression confers cross resistance to PARP inhibitor and cisplatin, and shorter progression free survival in ovarian cancer patients. In contrast, loss of THAP1 in BRCA2 deficient cells increases genome instability and correlates with improved responses to chemotherapy. Pathogenic THAP1 mutations are causatively linked to adult-onset torsion dystonia type 6 (DYT6) movement disorder, but the critical disease targets are unknown. We further demonstrate that murine models of Thap1-associated dystonia show reduced Shld1 expression concomitant with elevated levels of unresolved DNA damage in the brain. In summary, our study provides the first example of a transcriptional network that directly controls DSB repair choice and reveals a previously unsuspected link between DNA damage and dystonia.
2021-04-13 | GSE154728 | GEO