CTCF

CTCF
  • 文章类型: Journal Article
    在三维(3D)核空间中,基因组组织成一系列有序的结构,对基因调控产生重要影响。T淋巴细胞,适应性免疫反应的关键参与者,激活后经历复杂的转录重塑,导致分化为特异性效应和记忆T细胞亚群。最近的证据表明,T细胞活化伴随着基因组结构在多个水平上的动态变化。为探索3D基因组组织的功能相关性和分子机制提供了独特的生物学背景。这里,我们总结了最近的进展,将基因组结构的重组与转录程序的重塑以及T细胞活化和分化过程中细胞命运的转换联系起来。我们进一步讨论各种染色质结构调节剂,包括CCCTC结合因子和几种转录因子,在这个过程中共同调节基因组结构。
    Within the three-dimensional (3D) nuclear space, the genome organizes into a series of orderly structures that impose important influences on gene regulation. T lymphocytes, crucial players in adaptive immune responses, undergo intricate transcriptional remodeling upon activation, leading to differentiation into specific effector and memory T cell subsets. Recent evidence suggests that T cell activation is accompanied by dynamic changes in genome architecture at multiple levels, providing a unique biological context to explore the functional relevance and molecular mechanisms of 3D genome organization. Here, we summarize recent advances that link the reorganization of genome architecture to the remodeling of transcriptional programs and conversion of cell fates during T cell activation and differentiation. We further discuss how various chromatin architecture regulators, including CCCTC-binding factor and several transcription factors, collectively modulate the genome architecture during this process.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    目的:本研究旨在探讨程序性细胞死亡配体1(PD-L1)通过介导CCCTC结合因子(CTCF)表达促进人牙髓干细胞(hDPSCs)增殖和成骨分化的作用及其机制。
    方法:通过免疫共沉淀法验证PD-L1与CTCF的相互作用。用脂多糖或成骨诱导培养基处理用PD-L1过表达和CTCF敲低载体转染的hDPSC。检测炎性细胞因子和骨/牙源性分化相关基因。使用碱性磷酸酶(ALP)和茜素红S染色评估hDPSC的骨/牙源性分化。
    结果:PD-L1过表达抑制LPS诱导的促炎细胞因子上调,细胞增殖,ALP活性,和钙在hDPSC中的沉积,并提高了骨/牙源性分化相关基因的表达;然而,这种表达模式可以通过CTCF敲低逆转。免疫共沉淀结果证实了PD-L1与CTCF的结合,表明hDPSC中PD-L1过表达增加CTCF表达,从而抑制炎症反应并增加hDPSC的骨/牙源性分化。
    结论:PD-L1在hDPSC中的过表达增强了hDPSC的增殖和骨/牙源性分化,并通过上调CTCF表达来抑制炎症反应。
    OBJECTIVE: The aim of this study was to explore the effect and mechanism of programmed cell death ligand 1 (PD-L1) in promoting the proliferation and osteo/odontogenic-differentiation of human dental pulp stem cells (hDPSCs) by mediating CCCTC-binding factor (CTCF) expression.
    METHODS: The interaction between PD-L1 and CTCF was verified through co-immunoprecipitation. hDPSCs transfected with PD-L1 overexpression and CTCF knockdown vectors were treated with lipopolysaccharide or an osteogenic-inducing medium. Inflammatory cytokines and osteo/odontogenic-differentiation related genes were measured. Osteo/odontogenic-differentiation of hDPSCs was assessed using alkaline phosphatase (ALP) and alizarin red S staining.
    RESULTS: Overexpression of PD-L1 inhibited LPS-induced pro-inflammatory cytokine upregulation, cell proliferation, ALP activity, and calcium deposition in hDPSCs and elevated the expression of osteo/odontogenic-differentiation related genes; however, such expression patterns could be reversed by CTCF knockdown. Co-immunoprecipitation results confirmed the binding of PD-L1 to CTCF, indicating that PD-L1 overexpression in hDPSCs increases CTCF expression, thus inhibiting the inflammatory response and increasing osteo/odontogenic-differentiation of hDPSCs.
    CONCLUSIONS: PD-L1 overexpression in hDPSCs enhances the proliferation and osteo/odontogenic-differentiation of hDPSCs and inhibit the inflammatory response by upregulating CTCF expression.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    转录因子(TF)在染色质上的停留转化为基因组上的定量转录或结构结果。常用的甲醛交联累积地固定TF-DNA相互作用并损害测量的占有率水平。在这里,我们绘制了CTCF和MAZ等全球或单个锌指TF的占用水平,以高分辨率的脚印形式,天然染色质。通过结合增强扰动条件,我们建立了S分数,一种定量指标,用于替代天然染色质上不同基序之间CTCF或MAZ保留的连续性。保留有天然染色质的CTCF位点具有CTCF基序内的序列特征,S评分比从其他交联或天然测定获得的指标更好地解释。CTCF在天然染色质上的保留与局部SUMO化水平相关,和抗相关的转录活性。S分数成功地描绘了CTCF介导的染色质结构的其他掩蔽差异稳定性,或独立于CTCF的MAZ。总的来说,我们的研究建立了跨天然染色质结合位点的TF保留的范式连续体,解释动态基因组组织。
    Transcription factor (TF) residence on chromatin translates into quantitative transcriptional or structural outcomes on genome. Commonly used formaldehyde crosslinking fixes TF-DNA interactions cumulatively and compromises the measured occupancy level. Here we mapped the occupancy level of global or individual zinc finger TFs like CTCF and MAZ, in the form of highly resolved footprints, on native chromatin. By incorporating reinforcing perturbation conditions, we established S-score, a quantitative metric to proxy the continuum of CTCF or MAZ retention across different motifs on native chromatin. The native chromatin-retained CTCF sites harbor sequence features within CTCF motifs better explained by S-score than the metrics obtained from other crosslinking or native assays. CTCF retention on native chromatin correlates with local SUMOylation level, and anti-correlates with transcriptional activity. The S-score successfully delineates the otherwise-masked differential stability of chromatin structures mediated by CTCF, or by MAZ independent of CTCF. Overall, our study established a paradigm continuum of TF retention across binding sites on native chromatin, explaining the dynamic genome organization.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    喉鳞状细胞癌(LSCC)在头颈部鳞状细胞癌中死亡率最高。本研究旨在研究长链非编码RNA(lncRNA)MSC反义RNA1(MSC-AS1)对LSCC发育的生物学作用及其潜在机制。在生物信息学工具中预测头颈部鳞状细胞癌中lncRNAs的表达和预后价值。MSC-AS1在LSCC患者中的过表达预测预后不良。使用shRNA耗尽MSC-AS1抑制了AMC-HN-8和TU-177细胞的恶性表型。MSC-AS1,主要位于细胞核,与转录因子CCCTC结合因子(CTCF)密切相关。CTCF在体外和体内均具有抗肿瘤作用。Ataxin-7(ATXN7)被预测为CTCF的下游靶标,其表达受MSC-AS1负控制。发现MSC-AS1阻断CTCF的表达,从而抑制ATXN7。最后,LSCC中的MSC-AS1过表达受含有YTH结构域的蛋白1(YTHDC1)介导的m6A修饰控制。总之,我们的研究确定了YTHDC1/MSC-AS1/CTCF/ATXN7轴在LSCC发展,这表明MSC-AS1是LSCC治疗中具有吸引力的生物标志物。
    Laryngeal squamous cell carcinoma (LSCC) has the highest mortality rate among head and neck squamous cell carcinoma. This study was designed to investigate the biological effect of long noncoding RNA (lncRNA) MSC antisense RNA 1 (MSC-AS1) on LSCC development and the underlying mechanism. The expression and prognostic value of lncRNAs in head and neck squamous cell carcinoma were predicted in the bioinformatics tools. The overexpression of MSC-AS1 in LSCC patients predicted a poor prognosis. Depletion of MSC-AS1 using shRNA repressed the malignant phenotype of AMC-HN-8 and TU-177 cells. MSC-AS1, mainly localized in the nucleus, interacted closely with the transcription factor CCCTC-binding factor (CTCF). CTCF played anti-tumor effects in vitro and in vivo. Ataxin-7 (ATXN7) was predicted to be a downstream target of CTCF, whose expression was negatively controlled by MSC-AS1. MSC-AS1 was found to block the expression of CTCF, thereby repressing ATXN7. Finally, MSC-AS1 overexpression in LSCC was governed by YTH domain-containing protein 1 (YTHDC1)-mediated m6A modification. In summary, our research identified the YTHDC1/MSC-AS1/CTCF/ATXN7 axis in LSCC development, which indicated that MSC-AS1 is an attractive biomarker in the LSCC treatment.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    CTCF对早期胚胎发育中的染色质结构和转录调控至关重要。然而,CTCF染色质在植入前胚胎中占据的动力学仍不清楚.在这项研究中,我们使用CUT&RUN技术调查小鼠植入前发育中CTCF的占有率。我们的发现表明,CTCF在合子基因组激活(ZGA)之前开始与基因组结合,偏爱CTCF锚定染色质环。尽管CTCF的大部分入住率一直保持不变,我们确定了一组富含小鼠特异性短散布元件(SINE)家族B2的特定结合位点,这些结合位点仅限于裂解阶段。值得注意的是,我们发现神经保护蛋白ADNP抵消了CTCF在SINEB2衍生的CTCF结合位点的稳定缔合作用.合子中Adnp的敲除导致CTCF结合信号恢复受损,H3K9me3的沉积失败,以及在桑态度胚到胚泡的转变过程中SINEB2的转录抑制,这进一步导致植入周围胚胎的不忠实细胞分化。我们的分析强调了植入前胚胎细胞分化过程中CTCF结合的ADNP依赖性限制。此外,我们的研究结果揭示了转座因子(TE)在促进遗传创新和积极塑造哺乳动物特有的早期胚胎发育过程中的功能重要性.
    CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF-anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short interspersed element (SINE) family B2 that are restricted to the cleavage stages. Notably, we discovered that the neuroprotective protein ADNP counteracts the stable association of CTCF at SINE B2-derived CTCF-binding sites. Knockout of Adnp in the zygote led to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 during the morula-to-blastocyst transition, which further led to unfaithful cell differentiation in embryos around implantation. Our analysis highlights an ADNP-dependent restriction of CTCF binding during cell differentiation in preimplantation embryos. Furthermore, our findings shed light on the functional importance of transposable elements (TEs) in promoting genetic innovation and actively shaping the early embryo developmental process specific to mammals.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    CTCF介导的染色质环创建了限制启动子-增强子相互作用的绝缘邻域,作为基因调控的一个单位。CTCF结合位点(CBS)的破坏将导致绝缘社区的破坏,这反过来会导致所含基因的失调。在最近的一项研究中,发现CTCF/粘附素结合位点是癌症基因组中的主要突变热点。突变可以影响CTCF结合,造成绝缘社区的破坏。我们的分析显示,在具有特定发生在锚定区域的突变的绝缘社区中,众所周知的原癌基因显着富集。可以假设一些突变破坏CTCF结合,导致绝缘社区的破坏,并随后激活这些绝缘社区内的原癌基因。为了探索这种突变的后果,我们开发DeepCBS,一种能够分析CTCF结合位点突变的计算工具,预测他们对绝缘社区的影响,并研究原癌基因的潜在激活。Futhermore,DeepCBS应用于肝癌的体细胞突变数据。因此,鉴定了破坏CTCF结合位点的87个突变,这导致鉴定出237个被破坏的绝缘社区,总共包含135个基因。对肝癌中基因表达差异的整合分析进一步突出了三个基因:ARHGEF39,UBE2C和DQX1。其中,ARHGEF39和UBE2C已在文献中报道为参与肝癌发展的潜在癌基因。结果表明,DQX1可能是肝癌的潜在癌基因,可能有助于肿瘤的免疫逃逸。总之,DeepCBS是一种有前途的方法,用于分析CTCF结合位点发生的突变对CTCF绝缘子功能的影响。具有潜在的扩展,以阐明突变对CTCF其他功能的影响。
    CTCF-mediated chromatin loops create insulated neighborhoods that constrain promoter-enhancer interactions, serving as a unit of gene regulation. Disruption of the CTCF binding sites (CBS) will lead to the destruction of insulated neighborhoods, which in turn can cause dysregulation of the contained genes. In a recent study, it is found that CTCF/cohesin binding sites are a major mutational hotspot in the cancer genome. Mutations can affect CTCF binding, causing the disruption of insulated neighborhoods. And our analysis reveals a significant enrichment of well-known proto-oncogenes in insulated neighborhoods with mutations specifically occurring in anchor regions. It can be assumed that some mutations disrupt CTCF binding, leading to the disruption of insulated neighborhoods and subsequent activation of proto-oncogenes within these insulated neighborhoods. To explore the consequences of such mutations, we develop DeepCBS, a computational tool capable of analyzing mutations at CTCF binding sites, predicting their influence on insulated neighborhoods, and investigating the potential activation of proto-oncogenes. Futhermore, DeepCBS is applied to somatic mutation data of liver cancer. As a result, 87 mutations that disrupt CTCF binding sites are identified, which leads to the identification of 237 disrupted insulated neighborhoods containing a total of 135 genes. Integrative analysis of gene expression differences in liver cancer further highlights three genes: ARHGEF39, UBE2C and DQX1. Among them, ARHGEF39 and UBE2C have been reported in the literature as potential oncogenes involved in the development of liver cancer. The results indicate that DQX1 may be a potential oncogene in liver cancer and may contribute to tumor immune escape. In conclusion, DeepCBS is a promising method to analyze impacts of mutations occurring at CTCF binding sites on the insulator function of CTCF, with potential extensions to shed light on the effects of mutations on other functions of CTCF.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    卵巢癌是最常见的妇科恶性肿瘤之一,预后差,缺乏有效的治疗手段。卵巢癌状况的改善迫切需要探索其分子机制以开发更有效的分子靶向药物。在这项研究中,人核糖体蛋白l35a(RPL35A)在体外和体内卵巢癌中的作用。我们的数据确定RPL35A表达在卵巢癌中异常升高。临床上,RPL35A高表达可预测卵巢癌患者生存期短、TNM分期差.功能上,RPL35A敲低抑制卵巢癌细胞增殖和迁移,细胞凋亡增强,而过表达具有相反的效果。机械上,RPL35A促进转录因子YY1与卵巢癌细胞CTCF的直接结合。始终如一,RPL35A在体外和体内取决于CTCF调节卵巢癌进展。此外,RPL35A通过PPAR通路影响卵巢癌细胞的增殖和凋亡。总之,RPL35A通过促进YY1和CTCF启动子的结合来驱动卵巢癌进展,而抑制这一过程可能是靶向治疗该疾病的有效策略。
    Ovarian cancer is one of the most common gynaecological malignancies with poor prognosis and lack of effective treatment. The improvement of the situation of ovarian cancer urgently requires the exploration of its molecular mechanism to develop more effective molecular targeted drugs. In this study, the role of human ribosomal protein l35a (RPL35A) in ovarian cancer was explored in vitro and in vivo. Our data identified that RPL35A expression was abnormally elevated in ovarian cancer. Clinically, high expression of RPL35A predicted short survival and poor TNM staging in patients with ovarian cancer. Functionally, RPL35A knock down inhibited ovarian cancer cell proliferation and migration, enhanced apoptosis, while overexpression had the opposite effect. Mechanically, RPL35A promoted the direct binding of transcription factor YY1 to CTCF in ovarian cancer cells. Consistently, RPL35A regulated ovarian cancer progression depending on CTCF in vitro and in vivo. Furthermore, RPL35A affected the proliferation and apoptosis of ovarian cancer cells through PPAR signalling pathway. In conclusion, RPL35A drove ovarian cancer progression by promoting the binding of YY1 and CTCF promoter, and inhibiting this process may be an effective strategy for targeted therapy of this disease.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目的:我们的研究旨在阐明RNA解旋酶DEAD-Box解旋酶17(DDX17)在NAFLD中的作用并探讨其潜在机制。
    方法:我们创建了肝细胞特异性Ddx17缺陷小鼠,旨在研究Ddx17对成年雄性小鼠高脂饮食(HFD)以及蛋氨酸和胆碱缺乏的1-氨基酸饮食(MCD)诱导的NAFLD的影响。进行RNA-seq和脂质组学分析以描绘代谢景观,和CUT&Tag结合染色质免疫沉淀(ChIP)和荧光素酶报告基因测定进行。
    结果:在这项工作中,我们观察到DDX17在NASH患者肝脏和HFD或MCD诱导的NASH小鼠模型中的表达显著增加.在将慢病毒导入肝细胞L02用于DDX17敲低或过表达后,我们发现,由棕榈酸/油酸(PAOA)诱导的L02细胞中的脂质积累被DDX17敲低明显减弱,但DDX17过表达增强。此外,肝细胞特异性DDX17基因敲除可显着缓解肝脏脂肪变性,MCD和HFD给药后小鼠的炎症反应和纤维化。机械上,我们对RNA-seq和CUT&Tag结果结合ChIP和荧光素酶报告基因分析的分析表明,DDX17通过与CCCTC结合因子(CTCF)和DEAD-Box解旋酶5(DDX5)合作转录抑制Cyp2c29基因表达.使用绝对定量脂质组学分析,我们确定了肝细胞特异性DDX17缺陷,该缺陷降低了MCD给药后小鼠肝脏的脂质积累和脂质组成改变.基于RNA-seq分析,我们的研究结果表明,DDX17可能对小鼠NASH模型中脂质代谢的调节和M1巨噬细胞的活化产生潜在影响.
    结论:这些结果表明,DDX17通过促进肝细胞中的脂质积累参与NASH的发展,诱导M1巨噬细胞的激活,通过Cyp2c29的转录抑制小鼠随后的炎症反应和纤维化。因此,DDX17有望成为治疗NASH的潜在药物靶标。
    Our study was to elucidate the role of RNA helicase DEAD-Box Helicase 17 (DDX17) in NAFLD and to explore its underlying mechanisms.
    We created hepatocyte-specific Ddx17-deficient mice aim to investigate the impact of Ddx17 on NAFLD induced by a high-fat diet (HFD) as well as methionine and choline-deficient l-amino acid diet (MCD) in adult male mice. RNA-seq and lipidomic analyses were conducted to depict the metabolic landscape, and CUT&Tag combined with chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted.
    In this work, we observed a notable increase in DDX17 expression in the livers of patients with NASH and in murine models of NASH induced by HFD or MCD. After introducing lentiviruses into hepatocyte L02 for DDX17 knockdown or overexpression, we found that lipid accumulation induced by palmitic acid/oleic acid (PAOA) in L02 cells was noticeably weakened by DDX17 knockdown but augmented by DDX17 overexpression. Furthermore, hepatocyte-specific DDX17 knockout significantly alleviated hepatic steatosis, inflammatory response and fibrosis in mice after the administration of MCD and HFD. Mechanistically, our analysis of RNA-seq and CUT&Tag results combined with ChIP and luciferase reporter assays indicated that DDX17 transcriptionally represses Cyp2c29 gene expression by cooperating with CCCTC binding factor (CTCF) and DEAD-Box Helicase 5 (DDX5). Using absolute quantitative lipidomics analysis, we identified a hepatocyte-specific DDX17 deficiency that decreased lipid accumulation and altered lipid composition in the livers of mice after MCD administration. Based on the RNA-seq analysis, our findings suggest that DDX17 could potentially have an impact on the modulation of lipid metabolism and the activation of M1 macrophages in murine NASH models.
    These results imply that DDX17 is involved in NASH development by promoting lipid accumulation in hepatocytes, inducing the activation of M1 macrophages, subsequent inflammatory responses and fibrosis through the transcriptional repression of Cyp2c29 in mice. Therefore, DDX17 holds promise as a potential drug target for the treatment of NASH.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:普遍使用替代启动子会导致癌变过程中基因表达的失调,并可能推动精子发生中新基因的出现。然而,关于支持替代启动子激活的机制知之甚少。
    结果:这里我们描述了癌症-睾丸特异性转录是如何被激活的。我们显示了基因间和内含子CTCF结合位点,在正常体细胞中转录惰性,可以在胚芽和癌细胞中表观遗传学重编程为活跃的从头启动子。BORIS/CTCFL,广泛表达的CTCF的睾丸特异性旁系,触发CTCF位点的表观遗传重编程为活性转录单元。BORIS结合启动了染色质重塑因子的募集,SRCAP,然后用H2A替换H2A组蛋白。Z,导致CTCF结合位点侧翼的核小体中更松弛的染色质状态。CTCF结合位点周围染色质的松弛促进了多种其他转录因子的募集。从而激活从给定结合位点的转录。我们证明了表观遗传重编程的CTCF结合位点可以驱动癌症睾丸基因的表达,长链非编码RNA,逆转录伪基因,和休眠的转座因子。
    结论:因此,BORIS作为一种转录因子,表观遗传重编程聚集的CTCF结合位点进入转录起始位点,促进生殖细胞和癌细胞中替代启动子的转录。
    Pervasive usage of alternative promoters leads to the deregulation of gene expression in carcinogenesis and may drive the emergence of new genes in spermatogenesis. However, little is known regarding the mechanisms underpinning the activation of alternative promoters.
    Here we describe how alternative cancer-testis-specific transcription is activated. We show that intergenic and intronic CTCF binding sites, which are transcriptionally inert in normal somatic cells, could be epigenetically reprogrammed into active de novo promoters in germ and cancer cells. BORIS/CTCFL, the testis-specific paralog of the ubiquitously expressed CTCF, triggers the epigenetic reprogramming of CTCF sites into units of active transcription. BORIS binding initiates the recruitment of the chromatin remodeling factor, SRCAP, followed by the replacement of H2A histone with H2A.Z, resulting in a more relaxed chromatin state in the nucleosomes flanking the CTCF binding sites. The relaxation of chromatin around CTCF binding sites facilitates the recruitment of multiple additional transcription factors, thereby activating transcription from a given binding site. We demonstrate that the epigenetically reprogrammed CTCF binding sites can drive the expression of cancer-testis genes, long noncoding RNAs, retro-pseudogenes, and dormant transposable elements.
    Thus, BORIS functions as a transcription factor that epigenetically reprograms clustered CTCF binding sites into transcriptional start sites, promoting transcription from alternative promoters in both germ cells and cancer cells.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    转录因子ZNF143在串联阵列中包含七个锌指的中心结构域,并参与3D基因组构建。然而,ZNF143在染色质循环中起作用的机制尚不清楚.这里,我们显示ZNF143直接在增强子和启动子内定向识别各种基因组位点,并且是这些位点之间染色质循环所必需的。此外,ZNF143位于众多CTCF站点的CTCF和cohesin之间,和ZNF143去除缩小了CTCF和cohesin之间的空间。此外,ZNF143的遗传缺失,与急性CTCF降解相结合,揭示ZNF143和CTCF协同调控高阶拓扑染色质组织。最后,CTCF耗尽扩大了直接的ZNF143染色质循环。因此,ZNF143被CTCF招募到CTCF位点,以调节CTCF/相干蛋白构型和TAD(拓扑关联域)的形成,而ZNF143本身直接对基因组DNA基序的定向识别通过染色质循环调节启动子活性。
    The transcription factor ZNF143 contains a central domain of seven zinc fingers in a tandem array and is involved in 3D genome construction. However, the mechanism by which ZNF143 functions in chromatin looping remains unclear. Here, we show that ZNF143 directionally recognizes a diverse range of genomic sites directly within enhancers and promoters and is required for chromatin looping between these sites. In addition, ZNF143 is located between CTCF and cohesin at numerous CTCF sites, and ZNF143 removal narrows the space between CTCF and cohesin. Moreover, genetic deletion of ZNF143, in conjunction with acute CTCF degradation, reveals that ZNF143 and CTCF collaborate to regulate higher-order topological chromatin organization. Finally, CTCF depletion enlarges direct ZNF143 chromatin looping. Thus, ZNF143 is recruited by CTCF to the CTCF sites to regulate CTCF/cohesin configuration and TAD (topologically associating domain) formation, whereas directional recognition of genomic DNA motifs directly by ZNF143 itself regulates promoter activity via chromatin looping.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

公众号