更新于：2024-09-19

POU4F2

更新于：2024-09-19

基本信息

别名

Brain-3B、Brain-specific homeobox/POU domain protein 3B、Brn-3b

+ [4]

简介

Tissue-specific DNA-binding transcription factor involved in the development and differentiation of target cells (PubMed:19266028, PubMed:23805044). Functions either as activator or repressor modulating the rate of target gene transcription through RNA polymerase II enzyme in a promoter-dependent manner (PubMed:19266028, PubMed:23805044). Binds to the consensus octamer motif 5'-AT[A/T]A[T/A]T[A/T]A-3' of promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Binds to an octamer site to form a ternary complex with ISL1; cooperates positively with ISL1 and ISL2 to potentiate transcriptional activation of RGC target genes being involved in RGC fate commitment in the developing retina and RGC axon formation and pathfinding. Inhibits DLX1 and DLX2 transcriptional activities preventing DLX1- and DLX2-mediated ability to promote amacrine cell fate specification. In cooperation with TP53 potentiates transcriptional activation of BAX promoter activity increasing neuronal cell apoptosis. Negatively regulates BAX promoter activity in the absence of TP53. Acts as a transcriptional coactivator via its interaction with the transcription factor ESR1 by enhancing its effect on estrogen response element (ERE)-containing promoter. Antagonizes the transcriptional stimulatory activity of POU4F1 by preventing its binding to an octamer motif. Involved in TNFSF11-mediated terminal osteoclast differentiation (By similarity).

关联

100 项与 POU4F2 相关的临床结果

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100 项与 POU4F2 相关的转化医学

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0 项与 POU4F2 相关的专利（医药）

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255

项与 POU4F2 相关的文献（医药）

2024-09-01·Life Sciences

Intervention of epithelial mesenchymal transition against colon cancer cell growth and metastasis based on SOX21/POU4F2/Hedgehog signaling axis

Article

作者: Zhang, Bo ; Wang, Peipei ; Yan, Yici ; Sun, Leitao ; Gao, Yangyang ; Zhou, Chenxi ; Cao, Qiaochang ; Yu, Jieru

AIMSColon cancer poses a major threat to human health and a heavy burden on the national economy. As a member of the SOX transcription factor family, SRY-box transcription factor 21 (SOX21) is associated with various cancers, but its mechanism of action in colon cancer remains unclear. This study focused on the molecular mechanisms of transcription factor SOX21 in proliferation and metastasis of colon cancer cells.MAIN METHODSWe analyzed SOX21 expression level and its impact on survival in colon cancer patients by bioinformatics analysis. We used public databases for gene correlation, GSEA enrichment analysis. Cell function experiments (colony formation assay, wound healing assay, Transwell migration and invasion assay) were utilized to determine the impact of SOX21 silencing and over-expression on cell proliferation and metastasis. The luciferase reporter assay, CUT&RUN-qPCR assay and Methylation Specific PCR were used to explore SOX21-POU class 4 homeobox 2 (POU4F2) molecular interactions. The molecular mechanisms were verified by Quantitative real-time PCR and Western blot analysis.KEY FINDINGSSOX21 is highly expressed and affects the overall survival of colon cancer patients. SOX21 can attenuates POU4F2 methylation state by binding with it. In addition, this interaction facilitate its transcriptional activation of Hedgehog pathway, mediates epithelial-mesenchymal transition (EMT), consequently promoting the proliferation and metastasis of colon cancer cells.SIGNIFICANCEOur study reveals that SOX21 is an oncogenic molecule and suggests its regulatory role in colon carcinogenesis and progression, providing new insights into the treatment of this disease.

2024-06-01·European Urology Focus

Diagnostic Test Accuracy of Urinary DNA Methylation-based Biomarkers for the Detection of Primary and Recurrent Bladder Cancer: A Systematic Review and Meta-analysis

Review

作者: Carvalho, João A ; Henriques, Teresa S ; Pereira Rodrigues, Pedro ; Jerónimo, Carmen ; Monteiro-Reis, Sara ; Silva-Ferreira, Mariana ; Henrique, Rui ; Salta, Sofia

BACKGROUND AND OBJECTIVEDiagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited sensitivity, resulting in a substantial burden. Thus, noninvasive biomarkers have been investigated, among which DNA methylation has shown promise. This systematic review and meta-analysis sought to assess the diagnostic accuracy of DNA methylation biomarkers reported in the literature for bladder cancer detection, pinpointing the most informative one.METHODSThe search for this systematic review and meta-analysis was conducted on PubMed, Scopus, and Cochrane Library for relevant studies published until December 31, 2022. A meta-analysis was performed using a random-effect model, to compute the pooled sensitivity and specificity of the markers. PROSPERO's registration ID for the study is CRD42023397703.KEY FINDINGS AND LIMITATIONSOut of the 2297 studies retrieved, 68 were included in the final analysis, despite considerable heterogeneity. These involved 12 696 participants, of whom 5557 were diagnosed with bladder cancer. Using diagnostic odds ratio (DOR) as a comparative measure, the five most promising markers (pooled sensitivity, specificity, and DOR) were SALL3 (61%, 97%, and 55.67, respectively), PENK (77%, 93%, and 47.90, respectively), ZNF154 (87%, 90%, and 45.07, respectively), VIM (82%, 90%, and 44.81, respectively), and POU4F2 (81%, 89%, and 34.89, respectively). Urinary cytology identified bladder cancer with 55% sensitivity, 92% specificity, and 14.37 DOR.CONCLUSIONS AND CLINICAL IMPLICATIONSDNA methylation biomarkers disclose high accuracy for bladder cancer detection in urine. Nonetheless, validation studies in different clinical settings are scarce, hampering clinical use. The identified biomarkers should be prioritized in future validation studies.PATIENT SUMMARYIn this meta-analysis, we include previously published studies that used urine samples of bladder cancer patients' from all around the globe. We were able to compare the diagnostic accuracy of noninvasive markers across different populations. We were able to conclude on the most promising DNA methylation markers to detect bladder cancer using urine.

2024-02-01·Twin Research and Human Genetics

DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins

Article

作者: Ning, Feng ; Zhang, Dongfeng ; Yao, Jie ; Wang, Weijing

AbstractObesity is an established risk factor for hypertension, but the mechanisms are only partially understood. We examined whether body mass index (BMI)-related DNA methylation (DNAm) variation would mediate the association of BMI with blood pressure (BP). We first conducted a genomewide DNA methylation analysis in monozygotic twin pairs to detect BMI-related DNAm variation and then evaluated the mediating effect of DNAm on the relationship between BMI and BP levels using the causal inference test (CIT) method and mediation analysis. Ontology enrichment analysis was performed for CpGs using the GREAT tool. A total of 60 twin pairs for BMI and systolic blood pressure (SBP) and 58 twin pairs for BMI and diastolic blood pressure (DBP) were included. BMI was positively associated with SBP (β = 1.86, p = .0004). The association between BMI and DNAm of 85 CpGs reached p < 1×10–4 level. Eleven BMI-related differentially methylated regions (DMRs) within LNCPRESS1, OGDHL, RNU1-44P, NPHS1, ECEL1P2, LLGL2, RNY4P15, MOGAT3, PHACTR3, and BAI2 were found. Of the 85 CpGs, 9 mapped to C10orf71-AS1, NDUFB5P1, KRT80, BAI2, ABCA2, PEX11G and FGF4 were significantly associated with SBP levels. Of the 9 CpGs, 2 within ABCA2 negatively mediated the association between BMI and SBP, with a mediating effect of −0.24 (95% CI [−0.65, −0.01]). BMI was also positively associated with DBP (β = 0.60, p = .0495). The association between BMI and DNAm of 193 CpGs reached p < 1×10−4 level. Twenty-five BMI-related DMRs within OGDHL, POU4F2, ECEL1P2, TTC6, SMPD4, EP400, TUBA1C and AGAP2 were found. Of the 193 CpGs, 33 mapped to ABCA2, ADORA2B, CTNNBIP1, KDM4B, NAA60, RSPH6A, SLC25A19 and STIL were significantly associated with DBP levels. Of the 33 CpGs, 12 within ABCA2, SLC25A19, KDM4B, PTPRN2, DNASE1, TFCP2L1, LMNB2 and C10orf71-AS1 negatively mediated the association between BMI and DBP, with a total mediation effect of −0.66 (95% CI [−1.07, −0.30]). Interestingly, BMI might also negatively mediate the association between the DNAm of most CpG mediators mentioned above and BP. The mediating effect of DNAm was also found when stratified by sex. In conclusion, DNAm variation may partially negatively mediate the association of BMI with BP. Our findings may provide new clues to further elucidate the pathogenesis of obesity to hypertension and identify new diagnostic biomarkers and therapeutic targets for hypertension.

项与 POU4F2 相关的新闻（医药）

2022-12-26

·生物谷

Science子刊：在成年小鼠视网膜中将视网膜米勒胶质细胞重编程为类似于视网膜神经节细胞的神经元

在一项新的研究中，研究人员首次发现非神经元细胞经过诱导后可以模拟小鼠眼睛中的特定神经节细胞。该进展有望有朝一日能为科学家们创造出一条治疗包括青光眼、黄斑变性和帕金森病在内的多种神经退行性疾病的新途径。眼睛中的神经退行性疾病导致失明，因为哺乳动物的神经系统缺乏再生能力。在其他脊椎动物中，如鱼类和两栖动物，视网膜能够取代失去的神经元并恢复视觉功能。米勒胶质细胞（müller glia）是脊椎动物视网膜的主要胶质细胞，可作为具有神经系统再生能力的物种中神经源性祖细胞的来源。然而，在哺乳动物的视网膜中，米勒胶质细胞对视网膜损伤的反应是炎症反应而不是再生反应。在一项新的研究中，美国华盛顿大学医学院生物结构教授Tom Reh及其研究团队首次发现非神经元细胞经过诱导后可以模拟小鼠眼睛中的特定神经节细胞。这一进展有望有朝一日能为科学家们创造出一条治疗包括青光眼、黄斑变性和帕金森病在内的多种神经退行性疾病的新途径。相关研究结果发表在2022年11月25日的Science Advances期刊上，论文标题为“Reprogramming Müller glia to regenerate ganglion-like cells in adult mouse retina with developmental transcription factors”。 Reh团队之前已发现小鼠视网膜组织中的胶质细胞经诱导后可以变成神经元。如今他们改进了这一过程，以生产特定的细胞。Reh说，“我们主要只能制造一种类型的神经元---双极神经元（bipolar neuron）。就像我们当时所说的，我们可以制造一种没有人因疾病而失去的神经元。因此，虽然这非常令人惊讶，但它也不是超级临床相关的。从那时起，我们一直在试图弄清楚，我们是否可以对哺乳动物的这一过程进行进一步修补，看看我们是否可以扩大可再生的神经元类型的范围。” 在过去的三年里，Reh团队研究了脊椎动物（比如斑马鱼）中具有再生能力的称为转录因子的蛋白。转录因子是与DNA结合并调节基因活性的蛋白。这反过来又控制着决定细胞结构和功能的蛋白的产生。此前，Reh团队学会了通过小鼠视网膜米勒胶质细胞过表达促神经因子Ascl1使之恢复到更原始的状态，即视网膜祖细胞。然后进一步的处理可以将所产生的视网膜祖细胞推向其他方向。 Pou4f2和/或Islet1刺激RGC样神经元的再生。图片来自Science Advances, 2022, doi:10.1126/sciadv.abq7219。在这项新的研究中，Reh团队测试了组合使用促神经因子Ascl1和其他的发育上重要的转录因子是否能够更加精确地将源自视网膜米勒胶质细胞的视网膜祖细胞变成特定的视网膜细胞。具体来说，他们探讨了Ascl1过表达与其他两种不同类型的转录因子---Islet1和Pou4f2---组合使用的效果。这两种不同类型的转录因子已被证明对发育中的视网膜的细胞命运决定很重要，其中Pou4f2对视网膜神经节细胞（RGC）分化是必要的，而Islet1对包括RGC在内的几种类型的视网膜神经元的发育很重要。他们发现，Pou4f2和Islet1以及Ascl1在成年小鼠米勒胶质细胞中的表达引导由米勒胶质细胞产生的一个神经元亚群走向类似于RGC的细胞命运。这些由米勒胶质细胞产生的RGC样神经元(i)可以用正常RGC的标志物进行免疫标记；(ii)通过单细胞RNA测序（scRNA-seq），具有与发育中的RGC相似的转录组；(iii)比单独由Ascl1产生的神经元具有更广泛的电生理特征，如动作电位；以及(iv)显示与发育中RGC相似的染色质易接近性模式。这些研究结果表明，组合使用与发育有关的转录因子，可以将源自米勒胶质细胞的神经再生导向特定的细胞类型。 Reh说，这种方法“有可能具有真正广泛的适用性，因为它的原理是使你的胶质细胞成为类似祖细胞的细胞，但如今你不只是让这种细胞做它想做的事情。你控制它并引导它进入特定的发育轨迹。我认为这将普遍适用于大脑修复和脊髓修复的其他领域。” （生物谷 Bioon.com）参考资料： Levi Todd et al. Reprogramming Müller glia to regenerate ganglion-like cells in adult mouse retina with developmental transcription factors. Science Advances, 2022, doi:10.1126/sciadv.abq7219.