Ask about this productRelated genes to: ZNF251 antibody
- Gene:
- ZNF251 NIH gene
- Name:
- zinc finger protein 251
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 8q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-11-30
- Date modifiied:
- 2015-08-27
Related products to: ZNF251 antibody
Related articles to: ZNF251 antibody
- We present a large-scale study of structural variation (SV) in the Qatari population, based on short-read whole-genome sequencing (WGS) of 6,141 individuals, identifying 153,946 variants across 5 classes reflecting the region's diversity and evolutionary history. Leveraging consanguinity and biobank phenotypes, we identify >180 putative gene knockouts, and use proteomics to show functional consequences in homozygotes. Conversely, 52 genes show significant depletion of homozygous deletions, eight of which cause severe pediatric disease or murine embryonic lethality. Examining phenotypic extremes uncovers several non-exonic homozygous deletions with large effect, including in SPIRE2 (creatinine), MAGI2 (leanness) and a chr19 microRNA cluster (extreme obesity). Further, SV-GWAS reveals gene-trait associations independent of SNPs, including at ACY1 (acetylation), SLC2A9 (uric acid), UGT1A8 (bilirubin) and ZNF251 (alanine aminotransferase). Notably, 3.2% of Qataris carry findings in medically actionable genes, one-third attributable to SVs. Our findings offer a rich SV reference for a globally understudied population, and demonstrate the utility of consanguineous biobanks for studying SVs in health and disease. All common SVs and tag-SNPs are provided as imputation resource. - Source: PubMed
Publication date: 2026/01/13
Aliyev ElbaySyed NajeebVisconti AlessiaAliyev TaghiBelkadi AzizGhorbani MohammadmersadRossi NiccolòNaeem HaroonGandhi Geethanjali DevadossThareja GauravAl-Maraghi AljaziAamer WaleedIbrahim Amal AbdulsalamShaath RulanAl-Ajli Farooq OmarRazali Rozaimi MohamadSedlazeck Fritz JDavila SoniaAkil AmmiraSuhre KarstenMokrab YounesFalchi MarioFakhro Khalid A - Epigenetic mechanisms such as DNA methylation are hypothesized to play a pivotal role in the pathogenesis of anxiety disorders and to predict as well as relate to treatment response. An epigenome-wide association study (EWAS) (Illumina MethylationEPIC BeadChip) was performed at baseline (BL), post-treatment (POST) and 6-month follow-up (FU) in the so far largest longitudinal sample of patients with anxiety disorders (N = 415) treated with exposure-based cognitive behavioral therapy (CBT), and in 315 healthy controls. Independent of comorbidity with depression, anxiety disorders were significantly (p ≤ 6.409E-08) associated with altered DNA methylation at 148 CpGs partly mapping to genes previously implicated in processes related to anxiety, brain disorders, learning or plasticity (e.g., GABBR2, GABRD, GAST, IL12RB2, LINC00293, LOC101928626, MFGE8, NOTCH4, PTPRN2, RIMBP2, SPTBN1) or in a recent cross-anxiety disorders EWAS (TAOK1) after pre-processing and quality control (N = 378 vs. N = 295). Furthermore, BL DNA methylation at seven and three CpGs, respectively, was suggestively (p < 1E-5) associated with treatment response at POST (ABCA7, ADRA2C, LTBR, RPSAP52, SH3RF3, SLC47A2, ZNF251) and FU (ADGRD1, PRSS58, USP47). Finally, suggestive evidence for dynamic epigenome-wide DNA methylation changes along with CBT response emerged at four CpGs from BL to FU (ADIPOR2, EIF3B, OCA2, TMCC1). The identification of epigenetic biomarkers may eventually aid in developing environment-based preventive strategies aimed at increasing resilience by providing deeper molecular insights into the mechanisms underlying anxiety disorders. Defining epigenetic signatures as predictors or key mechanisms in exposure-based interventions could pave the way for more targeted and personalized treatments for anxiety disorders. - Source: PubMed
Publication date: 2025/04/25
Domschke KatharinaSchiele Miriam ACrespo Salvador ÓscarZillich LeaLipovsek JanPittig AndreHeinig IngmarRidderbusch Isabelle CStraube BenjaminRichter JanHollandt MaikePlag JensFydrich ThomasKoelkebeck KatjaWeber HeikeLueken UlrikeDannlowski UdoMargraf JürgenSchneider SilviaBinder Elisabeth BStröhle AndreasRief WinfriedKircher TiloPauli PaulHamm AlfonsArolt VolkerHoyer JürgenWittchen Hans-UlrichErhardt-Lehmann AngelikaKöttgen AnnaSchlosser PascalDeckert Jürgen - Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a promising new class of agents that have demonstrated efficacy in treating various cancers, particularly those with BRCA1/2 mutations. Cancer-associated BRCA1/2 mutations disrupt DNA double-strand break (DSB) repair via homologous recombination (HR). PARP inhibitors (PARPis) have been used to trigger synthetic lethality in BRCA1/2-mutated cancer cells by promoting the accumulation of toxic DSBs. Unfortunately, resistance to PARPis is common and can occur through multiple mechanisms, including the restoration of HR and/or stabilization of replication forks. To gain a better understanding of the mechanisms underlying PARPis resistance, we conducted an unbiased CRISPR-pooled genome-wide library screen to identify new genes whose deficiency confers resistance to the PARPi olaparib. Our research revealed that haploinsufficiency of the ZNF251 gene, which encodes zinc finger protein 251, is associated with resistance to PARPis in various breast and ovarian cancer cell lines carrying BRCA1 mutations. Mechanistically, we discovered that ZNF251 haploinsufficiency leads to stimulation of RAD51-mediated HR repair of DSBs in olaparib-treated BRCA1-mutated cancer cells. Moreover, we demonstrated that a RAD51 inhibitor reversed PARPi resistance in ZNF251 haploinsufficient cancer cells harboring BRCA1 mutations. Our findings provide important insights into the mechanisms underlying PARPis resistance by highlighting the role of RAD51 in this phenomenon. - Source: PubMed
Publication date: 2025/01/31
Li HuanChatla SrinivasLiu XiaoleiTian ZhenVekariya UmeshkumarWang PengKim DongwookOctaviani StaciaLian ZhaoruiMorton GeorgeFeng ZijieYang DanSullivan-Reed KatherineChilders WayneYu XiangChitrala Kumaraswamy NaiduMadzo JozefSkorski TomaszHuang Jian - Poly (ADP-ribose) polymerase (PARP) inhibitors represent a promising new class of agents that have demonstrated efficacy in treating various cancers, particularly those that carry mutations. The cancer associated mutations disrupt DNA double strand break (DSB) repair by homologous recombination (HR). PARP inhibitors (PARPis) have been applied to trigger synthetic lethality in -mutated cancer cells by promoting the accumulation of toxic DSBs. Unfortunately, resistance to PARPis is common and can occur through multiple mechanisms, including the restoration of HR and/or the stabilization of replication forks. To gain a better understanding of the mechanisms underlying PARPi resistance, we conducted an unbiased CRISPR-pooled genome-wide library screen to identify new genes whose deficiency confers resistance to the PARPi olaparib. Our study revealed that ZNF251, a transcription factor, is a novel gene whose haploinsufficiency confers PARPi resistance in multiple breast and ovarian cancer lines harboring BRCA1 mutations. Mechanistically, we discovered that haploinsufficiency leads to constitutive stimulation of DNA-PKcs-dependent non-homologous end joining (NHEJ) repair of DSBs and DNA-PKcs-mediated fork protection in -mutated cancer cells (BRCA1mut + KD). Moreover, we demonstrated that DNA-PKcs inhibitors can restore PARPi sensitivity in BRCA1mut + KD cells and . Our findings provide important insights into the mechanisms underlying PARPi resistance and highlight the unexpected role of DNA-PKcs in this phenomenon. - Source: PubMed
Publication date: 2023/04/06
Li HuanChatla SrinivasLiu XiaoleiVekariya UmeshkumarKim DongwookWalt MatthewLian ZhaoruiMorton GeorgeFeng ZijieYang DanLiu HongjunReed KatherineChilders WayneYu XiangMadzo JozefChitrala Kumaraswamy NaiduSkorski TomaszHuang Jian - Aberrant activation of ERK signaling is a hallmark of lung cancer. Although constitutively activating mutations of EGFR and KRAS contribute to the hyperactivation of ERK1/2, other mechanisms remain elusive. In this study, the zinc finger protein ZNF251 was found to be upregulated in clinical lung cancer samples, and it promoted the growth of lung cancer cells and the growth of primary lung KPC cells from mouse models (Ad-Cre, Kras , and P53 ). In studying the molecular mechanism, ZNF251 was found to inhibit the expression of dual-specificity phosphatase 6, a negative regulator of ERK activation, by directly binding to its promoter region. Taken together, our data indicate the tumor-promoting effects of ZNF251 in lung cancer and suggest that ZNF251 is a therapeutic target. - Source: PubMed
Publication date: 2020/07/15
Zhong ChenxiChen ChunjiYao FengFang Wentao