ZHX2的研究进展

新型转录抑制因子ZHX2（zinc-fingers and homeoboxes 2,ZHX2）属于锌指和同源框（zinc-fingers and homeoboxes,ZHX）家族,广泛存在于各种组织细胞核内,发挥转录抑制作用。ZHX2与多发性骨髓瘤（multiple mye-loma,MM）和肝细胞癌（hepatocellular carcinoma,HCC）的发生发展密切相关。此外,ZHX2对肾脏疾病发展过程中基因表达的转录调控有重要作用。ZHX2亦参与大脑皮层发育过程中神经前体细胞维持的调控。     

转录因子AP-2的研究进展

转录因子 AP- 2家族是一类 DNA结合蛋白 ,以二聚体形式结合到 DNA丰富 GC的元件上 ,调控基因表达。本文综述了近年来对 AP- 2的分子结构、活性调控以及对细胞增殖、分化、胚胎发育和肿瘤发生过程的作用的研究进展     

真核普通转录因子

三类真核RNA聚合酶分别选择性地转录细胞核基因,其转录特异性并不决定于RNA聚合酶本身,而是取决于被转录基因的启动子元件及能识别并结合这些元件的普通转录因子,它们与RNA聚合酶相互作用,在启动子区组装成转录起始复合物,从而起动转录。已知的三类普通转录因子中,大多数为相应RNA聚合酶所专用,只有少数因子中的个别亚基是三类酶所通用。本文简述这三类普通转录因子的结构、性质及其在转录中的功能。     

转录因子GATA-2的研究进展

转录因子GATA-2是具有锌指结构的GATA家族中的一员，它在造血系统中广泛表达。且与造血细胞的分化、发育关系密切．GATA-2主要调控造血干／祖细胞的增殖和分化，亦可调控其他造血相关因子的表达，并与白血病等血液病的发生有一定的相关．     

转录因子Ets-1对P21WAF1/CIP1启动子的影响

目的：研究转录因子Ets-1对P21WAF1/CIP1启动子的调控作用。 方法:应用瞬时转染、荧光素酶活性测定的方法分析Ets-1对P21WAF1/CIP1启动子荧光素酶报告重组体活性的影响。 结果:荧光素酶活性测定发现Ets-1可以上调P21WAF1/CIP1转录。缺乏激活结构域的Ets-1不能激活P21WAF1/CIP1启动子。Ets-1选择性地作用于P21WAF1/CIP1启动子中-1350GGAA-1347 Ets元件，该元件的序列突变可降低基础表达和Ets-1诱导的P21WAF1/CIP1启动子依赖的表达。-1577GGAT-1574元件介导基础表达，但不介导Ets-1激活的P21WAF1/CIP1启动子依赖的表达。 结论:Ets-1通过-1350GGAA-1347元件调控P21WAF1/CIP1启动子转录。     

转录因子AP-2与肿瘤的研究进展

激活蛋白AP-2是一种序列特异性的转录因子,由AP-2α,AP-2β,AP-2γ,AP-2δ和AP-2ε等几个关系密切、结构保守的成员组成,参与细胞增殖分化、凋亡和癌变的调控.在多种不同类型肿瘤的发生、发展过程中,AP-2都存在异常表达,且与肿瘤预后有着密切的关系.同时,AP-2对肿瘤的调节具有抑癌或促癌的双向效应,这...     

转录因子MafG抑制Nrf2介导的SSAT转录活化

目的研究转录辅助因子MafG对SSAT启动子活性的影响。方法在M15[pREP4]大肠埃希菌中表达MafG和Nrf2,利用纯化的MafG和Nrf2基因重组蛋白以及标记的PRE探针进行EMSA以确定MafG/Nrf2二聚体结合PRE元件的能力,然后利用报告基因技术,分析MafG表达对Nrf2介导的SSAT启动子活化的影响。结果Nrf2/MafG杂二聚体具备与PRE元件结合的能力,在非小细胞性肺癌细胞株H157内,MafG高表达抑制Nrf2介导的SSAT转录活化。结论Nrf2/MafG二聚体负性调节SSAT基因表达。     

转录因子GATA-2的研究进展

转录因子GATA-2是具有锌指结构的GATA家族中的一员,它在造血系统中广泛表达,且与造血细胞的分化、发育关系密切.GATA-2主要调控造血干/祖细胞的增殖和分化,亦可调控其他造血相关因子的表达,并与白血病等血液病的发生有一定的相关.     

肝细胞癌中ZHX2基因启动子甲基化增强AFP的表达

目的探讨肝细胞癌中锌指和同源框2(ZHX2)基因启动子甲基化表达与血清AFP水平的关系,分析AFP基因的表达调控机制。方法以0.5、1.0及5.0μmol/L甲基化抑制剂5-氮杂脱氧胞苷(5-Aza-Dc)培养人肝癌细胞株HepG2,采用RT-PCR及Western blot法检测用药前后ZHX2及AFP基因的mRNA和蛋白表达差异。运用甲基化特异性PCR检测肝细胞癌组织38例中ZHX2基因启动子表达情况,分析其与血清AFP水平的关系。结果 HepG2可见少量ZHX2 mRNA扩增,未检测到ZHX2蛋白表达,而AFP却高表达;应用终浓度为1.0μmol/L和5.0μmol/L的5-Aza-Dc处理肝癌细胞6 d,ZHX2表达明显增加,而AFP却表达下调。血清AFP高于25 ng/mL肝细胞癌组织中ZHX2启动子甲基化51.6%,明显高于血清AFP小于25 ng/mL组(P<0.05)。结论 ZHX2基因启动子甲基化与AFP基因的表达有关。     

FasL对CD28基因启动子活性的抑制作用

目的探讨FasL对CD28基因启动子活性的影响，为研究凋亡信号在免疫衰老中的作用提供资料。方法采用MTY法和annexin V—FITC染色测定细胞凋亡，Northern blot检测CD28 mRNA的表达水平，构建CD28基因上游非编码区序列的报告基因载体，并瞬时转染Jurkat E6-1细胞后，用Luciferase检测报告基因启动子的活性。结果FasL在Jurkat E6-1细胞介导的凋亡可使CD28 mRNA水平降低。CD28启动子的有效序列在上游-400 bp的范围内，并且FasL介导的凋亡信号可明显降低CD28启动子活性。结论FasL介导的凋亡信号是CD28基因启动子活性降低的重要原因。     

肝细胞癌中ZHX2、NF-YA及AFP表达的相关关系

目的 检测肝细胞癌(hepatocellular carcinoma,HCC)组织中ZHX2、NF-YA及AFP mRNA和蛋白表达的相关关系.方法 采用RT-PCR及免疫组织化学方法检测HCC组织中ZHX2、NF-YA及AFP mRNA和蛋白的表达情况.结果 ZHX2 mRNA在AFP mRNA阴性的25例HCC组织中的表达率为52.0%,明显高于AFP mRNA阳性组织中的表达率(26.3%,P=0.038),ZHX2 mRNA与AFP mRNA表达呈负相关(OR=0.33);NF-YA mRNA与ZHX2 mRNA表达呈正相关(OR=31.429),而与AFP mRNA表达呈负相关关系(OR=0.308).AFP蛋白阴性的142例HCC组织中,ZHX2蛋白的表达率为23.9%,明显高于在AFP蛋白阳性组织中的表达率(12.8%,P=0.034);HCC组织中ZHX2蛋白与AFP蛋白表达呈负相关(P=0.018,r=-0.153).NF-YA蛋白在HCC组织中与ZHX2蛋白表达呈正相关(P=0.000,r=0.371),与AFP蛋白表达呈负相关(P=0.000,r=-0.497).结论 联合检测AFP和ZHX2蛋白将提高HCC的诊断率;ZHX2可能是通过NF-YA来调控AFP的表达.     

结直肠癌中ZHX2蛋白表达的检测及其临床病理意义

目的检测结直肠癌中ZHX2蛋白的表达情况,探讨ZHX2与结直肠癌的关系。方法利用免疫组化法分别检测73例结直肠癌组织及其对应的癌旁正常组织中的ZHX2蛋白的表达情况。结果 73例结直肠癌组织中ZHX2蛋白的阳性率为82.2%(60/73),癌旁正常组织中ZHX2蛋白的阳性率为94.5%(69/73),差异具有统计学意义(P<0.05)。在结直肠癌组织中,ZHX2蛋白的阳性表达与肿瘤的发生部位及分化程度有关(P<0.05),与性别、年龄、肿瘤大小、浸润深度、淋巴结转移及Dukes分期无关(P>0.05)。ZHX2(+)组患者的生存时间长于ZHX2(-)组(P<0.05)。结论 ZHX2作为一种转录抑制因子,可能参与结直肠癌的发生与演进,并有助于患者预后的判断。     

Role of transcriptional factor Nrf2 in the acute lung injury of mice

Objective: This study aimed to investigate the expression and role of Nrf2 in the acute lung injury (ALI) of mice. Methods: A total of 60 BABL/c mice were randomly divided into 2 groups: ALI group and control group. In ALI group, ALI was introduced by injection of LPS. Immunohistochemistry was performed to detect Nrf2 expression in the lung; Western blot assay was employed to detect the expression of Nrf2 in the lung homogenate; ELISA was conducted to detect the expression of Nrf2 in the lung homogenate and BALF. Results: As compared to control group, ALI mice had a high Nrf2 expression in the lung as shown in immunohistochemistry, and the Nrf2 expression in the lung homogenate and BALF also increased markedly (P<0.05). Conclusion: The Nrf2 expression increases in the lung and BALF of ALI mice, suggesting that Nrf2 is involved in the inflammation during ALI and may serve as a new target in the therapy of ALI.     

Variants of the ST6GALNAC2 promoter influence transcriptional activity and contribute to genetic susceptibility to IgA nephropathy

IgA nephropathy (IgAN) is a polygenic disorder. Increasing evidence has implicated that aberrant glycosylation of IgA1 molecules, including alpha2,6 sialic acid defects, are involved in the pathogenesis of IgAN. In the present study, we designed an association study to investigate polymorphisms of two important genes, ST6GALNAC2 and NEU1, which are involved in the sialylation of the IgA1 molecule, in the susceptibility to IgAN. A total of 670 patients with histologically proven IgAN and 494 healthy controls were enrolled. Screening of SNPs in the coding and promoter regions of the ST6GALNAC2 and NEU1 genes was performed by sequencing. ST6-SNP1 (c.-988A>G), ST6-SNP2 [rs3840858:D>I(CGGC), c.-450_-449insCGGC], ST6-SNP3 (rs1867561:C>G, c.-135C>G), and ST6-SNP7 (rs2304921:G>A, c.186+12G>A) in the ST6GALNAC2 gene were selected as tagging SNPs. Functional evaluations of targets were assayed by luciferase activity. The alpha2,6 sialic acid contents of serum IgA1 in 497 patients were analyzed. Our results demonstrated that the frequency of haplotype ADG in the promoter region of ST6GALNAC2 was significantly higher in IgAN patients than that in controls (p=0.0069; odds ratio [OR]=1.36; 95% confidence interval [CI], 1.08-1.72). Furthermore, the ADG haplotype was associated with the deficient degrees of alpha2,6 sialic acid of IgA1 molecules in IgAN patients (r=0.408, p=0.0035). The ADG haplotype conferred significantly reduced promoter activity compared with the most common haplotype GDG in vitro (196.43+/-21.55 vs. 258.41+/-46.25; p=0.002). In the present study, we identified for the first time the ADG haplotype in the ST6GALNAC2 gene as a functional regulatory variant that may contribute to the genetic susceptibility in a subset of patients in whom the desialylation of IgA1 molecules was the main causative pathogenesis of IgAN.