Ask about this productRelated genes to: JAZF1 antibody
- Gene:
- JAZF1 NIH gene
- Name:
- JAZF zinc finger 1
- Previous symbol:
- -
- Synonyms:
- TIP27, DKFZp761K2222, ZNF802
- Chromosome:
- 7p15.2-p15.1
- Locus Type:
- gene with protein product
- Date approved:
- 2006-10-05
- Date modifiied:
- 2018-02-13
Related products to: JAZF1 antibody
Related articles to: JAZF1 antibody
- Genome-wide association studies (GWAS) have identified >1,200 signals associated with type 2 diabetes (T2D), yet identifying functional variants remains challenging because the majority of them lie in noncoding regions of the genome and are in areas of high linkage disequilibrium (LD). While chromatin accessibility QTL (caQTL) and expression QTL (eQTL) analyses are useful for nominating regulatory mechanisms underlying GWAS signals, limitations still exist in pinpointing functional variants within regions of high LD. A complementary approach that has been less frequently applied is to focus on the allele-specific effect on chromatin accessibility at heterozygous single-nucleotide polymorphisms (SNPs), hereafter referred to as "allelic imbalance". We analyzed the allelic imbalance of reads generated from an assay for transposase-accessible chromatin with sequencing (ATAC-seq) across genotyped samples from 490 donors in T2D-relevant tissues: skeletal muscle, liver, pancreatic islets, adipose tissue, and relevant cell types. We identified 119,949 allelically imbalanced SNPs (FDR<0.05) across the genome. The allelic imbalance was often most prominent in one tissue and showed an enrichment overlapping with tissue-specific transcription factor (TF) binding footprints. Focusing on the 8,581 SNPs in previously published 99% credible sets from 338 T2D GWAS signals, we identified 256 imbalanced SNPs across 123 (36.4% of) signals, each showing allelic imbalance in at least one tissue or cell type. Of these, 71 signals contained only a single imbalanced SNP, representing excellent candidate causative variants. As a proof-of-concept, we showed that 23 of the 256 imbalanced SNPs were supported by allelic assays from previous studies. Further, we experimentally validated two imbalanced SNPs as likely functional variants: rs34584161 among a seven-SNP T2D credible set at the signal in islets and rs849134 among a 13-SNP credible set at the signal in liver. This study demonstrates the power of integrating ATAC-seq allelic imbalance (ASAI) with GWAS statistical fine-mapping to identify candidate functional regulatory variants from among tightly linked GWAS variants in disease-relevant tissues. While applied here in T2D, this approach represents a widely applicable high-throughput framework for refining the genetic architecture of complex traits. - Source: PubMed
Publication date: 2026/07/15
Narisu NarisuLi Hannah XRathbun Caleb J MVarshney ArushiSwift Amy JYan TingfenSinha NeelamCurrin Kevin WXue DongxiangRobertson Catherine CTaylor D LelandTaylor Henry JBeck AimeeLee Brian NWang LiBroadaway K AlaineWilson Emma PStringham HeatherSaramies JoukoLakka Timo ASpracklen Cassandra NScott Laura JStitzel Michael LTuomilehto JaakkoLaakso MarkkuKoistinen Heikki ABoehnke MichaelArda H EfsunChen ShuibingBiesecker Leslie GBonnycastle Lori LErdos Michael RMohlke Karen LParker Stephen C JCollins Francis S - Testicular receptor 4 (TR4, NR2C2) is an orphan nuclear receptor involved in the regulation of metabolism, inflammation, cardiovascular disease, and cancer. Accumulating evidence indicates that TR4 exhibits functional plasticity, exerting protective or pathogenic effects depending on tissue and disease context, and sometimes displaying opposing roles within the same disease. However, the mechanisms underlying this functional duality remain poorly understood. Recent studies indicate that TR4 activity is determined not only by the receptor itself but also by dynamic coregulatory networks. Through interactions with coactivators, corepressors, epigenetic regulators, and environmental signaling pathways, TR4 integrates metabolic cues to generate context-dependent transcriptional programs. Coactivator networks centered on PGC-1α, steroid receptor coactivator (SRC) family members, and CBP/p300 support oxidative metabolism and anti-inflammatory responses, whereas RIP140-, NCoR/SMRT-, and HDAC-associated networks promote lipid accumulation, chronic inflammation, fibrosis, and tumor progression. Regulators such as JAZF1 further influence TR4 activity by reshaping coregulator recruitment and target-gene selection. In this review, we summarize the structural basis of TR4 regulation and discuss how coregulatory network remodeling governs its functions in metabolic, cardiovascular, inflammatory, and malignant diseases. We propose that TR4 functions as a context-dependent transcriptional platform whose activities are defined by its coregulatory landscape, providing a framework for precision therapies. - Source: PubMed
Publication date: 2026/07/03
Liu YunlongYu QingCheng ShuyuanRen MengtianFu Xiuping - To investigate the pathological morphology, immunophenotype, and molecular genetic characteristics of recurrent low-grade endometrial stromal sarcoma (LG-ESS) through the analysis of paired primary and recurrent tumor samples. - Source: PubMed
Publication date: 2026/06/02
Li JingZhang LihongChen Tingting - The regulation of pro-opiomelanocortin (Pomc) expression by the testicular orphan receptor 4 (TR4) constitutes a critical mechanism underlying the pathogenesis of Cushing's disease (CD). Although the endogenous repressor juxtaposed with another zinc finger gene 1 (JAZF1) inhibits TR4 activity, its relatively low binding affinity (K = 2246 nM) limits its therapeutic potential. In this study, we employed an iterative structure-based lead optimization strategy to enhance the JAZF1 scaffold. Utilizing Discovery Studio for virtual screening, we conducted successive rounds of in silico saturation mutagenesis, ranging from single point to multi-site combinatorial substitutions, which were subsequently validated through incremental experimental binding assays. This recursive optimization process led to the identification of two triple-mutant JAZF1 peptides (V56L/A68Y/A69R and D67L/A68Y/A69R) exhibiting more than a 2,200-fold enhancement in TR4 binding affinity. These engineered peptides, along with high-affinity small molecules such as nilotinib (K = 4.83 nM), effectively downregulated Pomc expression and inhibited proliferation of AtT-20 tumor cells. Taken together, these findings suggest that the JAZF1-TR4-Pomc axis may serve as a potential therapeutic target for modulating adrenocorticotropic hormone (ACTH) hypersecretion in CD. - Source: PubMed
Publication date: 2026/06/15
Guoguo WangMeng Su - Soft tissue sarcomas (STS) exhibit profound molecular heterogeneity. While recurrent gene fusions hold significant diagnostic and therapeutic value-guiding treatment selection and identifying novel molecular targets-our understanding of their broader clinical implications remains limited. - Source: PubMed
Publication date: 2026/04/27
Remiszewski PiotrBobak KlaudiaPiątkowski JakubGolik PawełTysarowski AndrzejSeliga KatarzynaSpałek Mateusz JSzumera-Ciećkiewicz AnnaWągrodzki MichałRutkowski PiotrCzarnecka Anna M