Zinc finger homeobox-3 (ZFHX3) exerts genome-wide regulation of dailygene expression in the suprachiasmatic nucleus
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ABSTRACT:
PROVIDER: PRJNA1089097 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28314251.fastq.gz | Fastqsanger.gz | |||
| SRR28314252.fastq.gz | Fastqsanger.gz | |||
| SRR28314253.fastq.gz | Fastqsanger.gz | |||
| SRR28422712_1.fastq.gz | Fastqsanger.gz | |||
| SRR28422712_2.fastq.gz | Fastqsanger.gz |
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Project description:The mammalian suprachiasmatic nucleus (SCN), situated in the ventral hypothalamus, directs daily cellular and physiological 24-hr rhythms across the body. The cell-autonomous timing mechanism is based on a self-sustaining transcriptional-translational feedback loop (TTFL) that in turn co-ordinates the expression of clock-controlled genes (CCGs) that direct circadian programmes of SCN cellular activity. In the mouse, the transcription factor, ZFHX3 (zinc finger homeobox-3), is necessary for the development of the SCN and influences circadian behaviour in the adult. The molecular mechanisms by which ZFHX3 affects the SCN at transcriptome and genome levels are, however, poorly defined. Here, we used chromatin immunoprecipitation (ChIP-seq) to map the genomic localization of ZFHX3 sites in the SCN. In parallel, we conducted a comprehensive SCN RNA sequencing at six distinct times-of-day, and then compared the transcriptional profile between the control and ZFHX3-conditional null mutants. We show that the genome wide occupancy of ZFHX3 occurs predominantly around the gene transcription start site (TSS), co-localizing with the known histone modifications, and preferentially partnering with the core-clock TFs (CLOCK, BMAL1) to regulate the clock gene(s) transcription. Correspondingly, we show that the conditional loss of ZFHX3 in the adult has a dramatic effect on the SCN transcriptome, reducing the level of neuropeptides-encoding transcripts and abolishing rhythmic (24-h) oscillation of the clock TF, Bmal1. In addition, various TTFL genes and CCGs exhibited altered circadian expression profiles, consistent with the advanced daily behaviour under 12hr light- 12hr dark conditions. Taken together, these findings reveal the extensive genome-wide regulation conferred by ZFHX3 in the central clock that orchestrates daily timekeeping in mammals.
2025-03-01 | GSE261430 | GEO
Project description:The mammalian suprachiasmatic nucleus (SCN), situated in the ventral hypothalamus, directs daily cellular and physiological 24-hr rhythms across the body. The cell-autonomous timing mechanism is based on a self-sustaining transcriptional-translational feedback loop (TTFL) that in turn co-ordinates the expression of clock-controlled genes (CCGs) that direct circadian programmes of SCN cellular activity. In the mouse, the transcription factor, ZFHX3 (zinc finger homeobox-3), is necessary for the development of the SCN and influences circadian behaviour in the adult. The molecular mechanisms by which ZFHX3 affects the SCN at transcriptome and genome levels are, however, poorly defined. Here, we used chromatin immunoprecipitation (ChIP-seq) to map the genomic localization of ZFHX3 sites in the SCN. In parallel, we conducted a comprehensive SCN RNA sequencing at six distinct times-of-day, and then compared the transcriptional profile between the control and ZFHX3-conditional null mutants. We show that the genome wide occupancy of ZFHX3 occurs predominantly around the gene transcription start site (TSS), co-localizing with the known histone modifications, and preferentially partnering with the core-clock TFs (CLOCK, BMAL1) to regulate the clock gene(s) transcription. Correspondingly, we show that the conditional loss of ZFHX3 in the adult has a dramatic effect on the SCN transcriptome, reducing the level of neuropeptides-encoding transcripts and abolishing rhythmic (24-h) oscillation of the clock TF, Bmal1. In addition, various TTFL genes and CCGs exhibited altered circadian expression profiles, consistent with the advanced daily behaviour under 12hr light- 12hr dark conditions. Taken together, these findings reveal the extensive genome-wide regulation conferred by ZFHX3 in the central clock that orchestrates daily timekeeping in mammals.
2025-03-01 | GSE261429 | GEO
Project description:Zinc finger homeobox-3 (ZFHX3) exerts genome-wide regulation of dailygene expression in the suprachiasmatic nucleus [ChIP-seq]
| PRJNA1086934 | ENA
Project description:Zinc finger homeobox-3 (ZFHX3) exerts genome-wide regulation of dailygene expression in the suprachiasmatic nucleus [RNA-seq]
| PRJNA1086932 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-03-01 | GSE261795 | GEO
Project description:The androgen/androgen receptor (AR) signaling drives prostate development and prostatic carcinogenesis, whereas loss of the zinc finger homeobox 3 (ZFHX3) transcription factor attenuates prostate development and promotes prostatic tumorigenesis. The androgen/AR signaling upregulates the transcription of ZFHX3 in prostate cancer cells. However, whether and how ZFHX3 is involved in the function of AR signaling in prostate cancer cells is unknown. In this study, we first carried out RNA-seq analysis in C4-2B prostate cancer cells to detect what genes and signaling pathways are caused by the deletion of ZFHX3. Gene set enrichment analysis (GSEA) revealed that among the top altered hallmark gene sets after ZFHX3 deletion, only the one for androgen response was decreased, whereas those for TNFα, interferon γ, and inflammatory response were enriched. For the 27 genes indicative AR activities, as defined in a previous study, expression levels for 18 of the 27 genes were significantly changed by ZFHX3 loss. Fifteen of these 18 genes were downregulated, including classical AR target genes KLK3, FKBP5, and TMPRSS2.
2025-07-09 | GSE288366 | GEO
Project description:Zinc-finger homeobox 3 (ZFHX3, also known as ATBF1) suppresses prostatic tumorigenesis. ZFHX3 is frequently found to have numerous deletions in human prostate cancer (PCa). However, the underlying molecular function of ZFHX3 during prostatic tumorigenesis is not well understood. N6-methyladenosine (m6A) modification in RNA plays a critical role in the development of cancers; however, the relationship between ZFHX3 and m6A modification is largely unknown in PCa. In this study, we found that ZFHX3 knockdown decreased total m6A levels through enhancing the transcriptional activity of FTO in PCa cells. Importantly, FTO inhibition suppressed cell proliferation and rescued the promoting function of ZFHX3 knockdown on cell proliferation. In vivo, we verified that FTO was upregulated and ZFHX3 was decreased in PCa patients and that a high level of ZFHX3 is indispensable for low FTO expression and is correlated with better patient survival. Through transcriptome sequencing and Me-RIP sequencing, we revealed that E2F2 and CDKN2C were the direct targets of FTO-mediated m6A modification and ZFXH3 was required for the regulation of FTO on E2F2 and CDKN2C expression. Unexpectedly, we uncovered that ZFHX3 expression was in return regulated by FTO in a m6A-dependent way. These findings establish a novel crosstalk mechanism between ZFHX3 and FTO in prostatic tumorigenesis.
2023-10-31 | GSE244356 | GEO
Project description:A protein altering variant in the gene encoding zinc finger homeobox-3 (ZFHX3) has recently been associated with lower BMI in a human genome-wide association study. We investigated metabolic parameters in mice harboring a missense mutation in Zfhx3 (Zfhx3Sci/+ ) and looked for altered in situ expression of transcripts that are associated with energy balance in the hypothalamus to understand how ZFHX3 may influence growth and metabolic effects. One-year-old male and female Zfhx3Sci/+ mice weighed less, had shorter body length, lower fat mass, smaller mesenteric fat depots, and lower circulating insulin, leptin, and insulin-like growth factor-1 (IGF1) concentrations than Zfhx3+/+ littermates. In a second cohort of 9-20-week-old males and females, Zfhx3Sci/+ mice ate less than wildtype controls, in proportion to body weight. In a third cohort of female-only Zfhx3Sci/+ and Zfhx3+/+ mice that underwent metabolic phenotyping from 6 to 14 weeks old, Zfhx3Sci/+ mice weighed less and had lower lean mass and energy expenditure, but fat mass did not differ. We detected increased expression of somatostatin and decreased expression of growth hormone-releasing hormone and growth hormone-receptor mRNAs in the arcuate nucleus (ARC). Similarly, ARC expression of orexigenic neuropeptide Y was decreased and ventricular ependymal expression of orphan G protein-coupled receptor Gpr50 was decreased. We demonstrate for the first time an energy balance effect of the Zfhx3Sci mutation, likely by altering expression of key ARC neuropeptides to alter growth, food intake, and energy expenditure.
| S-EPMC7615594 | biostudies-literature
Project description:BackgroundThe previous genome-wide studies have shown that rs7193343 single-nucleotide polymorphism (SNP) in zinc finger homeobox 3 (ZFHX3) gene correlate with risk of atrial fibrillation (AF). However, the distribution of this SNP differs significantly among various populations. The present study was to investigate whether combined evidence shows the association between ZFHX3 rs7193343 SNP and the risk of AF in various populations.MethodsA systematic search of all studies published through Dec 2014 was conducted using the Medline, Embase, WanFang, ScienceDirect, CNKI, and OVID databases. The case-control studies that evaluated an association between rs7193343 SNP and risk of AF were identified. The association between the ZFHX3 rs7193343 SNP and AF susceptibility was assessed using genetic models.ResultsWe collected 10 comparisons from six studies for rs7193343 SNP, including 1037 cases and 4310 controls in Asian, 5583 cases and 38215 controls in Caucasian, and then performed an updated meta-analysis and subgroup analysis based on ethnicity. In overall population, the occurrence of AF was found to be associated with T-allelic of rs7193343 SNP in ZFHX3 (OR =1.17, 95% CI 1.10-1.26). In subgroup analysis, we observed there was significant association between T-allele of rs7193343 and risk of AF in Caucasian subgroups (OR =1.20, 95% CI 1.12-1.30), but no statistically significance (OR = 1.07, 95% CI 0.92-1.24) in Asian population.ConclusionIn Caucasian population, genetic variant rs7193343 SNP is associated with risk of AF in Caucasian population. However, no association is found in Asian population based on the current evidence. Further studies with larger sample size involving case-control populations with multiple ethnics are still required in the future.
| S-EPMC4480884 | biostudies-literature
Project description:BackgroundThe previous genome-wide studies have shown that rs7193343 single-nucleotide polymorphism (SNP) in zinc finger homeobox 3 (ZFHX3) gene correlate with risk of atrial fibrillation (AF). However, the distribution of this SNP differs significantly among various populations. The present study was to investigate whether combined evidence shows the association between ZFHX3 rs7193343 SNP and the risk of AF in various populations.MethodsA systematic search of all studies published through Dec 2014 was conducted using the Medline, Embase, WanFang, ScienceDirect, CNKI, and OVID databases. The case-control studies that evaluated an association between rs7193343 SNP and risk of AF were identified. The association between the ZFHX3 rs7193343 SNP and AF susceptibility was assessed using genetic models.ResultsWe collected 10 comparisons from six studies for rs7193343 SNP, including 1037 cases and 4310 controls in Asian, 5583 cases and 38215 controls in Caucasian, and then performed an updated meta-analysis and subgroup analysis based on ethnicity. In overall population, the occurrence of AF was found to be associated with T-allelic of rs7193343 SNP in ZFHX3 (OR =1.17, 95% CI 1.10-1.26). In subgroup analysis, we observed there was significant association between T-allele of rs7193343 and risk of AF in Caucasian subgroups (OR =1.20, 95% CI 1.12-1.30), but no statistically significance (OR = 1.07, 95% CI 0.92-1.24) in Asian population.ConclusionIn Caucasian population, genetic variant rs7193343 SNP is associated with risk of AF in Caucasian population. However, no association is found in Asian population based on the current evidence. Further studies with larger sample size involving case-control populations with multiple ethnics are still required in the future.
| S-EPMC4480884 | biostudies-literature