piRNA生物学起源及功能研究进展

piRNA属于非编码小RNA的一员,常见于生殖系干细胞中.既往学者们认为它主要在维持干细胞功能、配子的形成以及沉默外来转座子等方面发挥作用.但近来在体细胞系中的发现,使得人们对它的生物起源以及功能行使有了更大的兴趣.就piRNA的发现、结构特征、功能与基因调控等进行了综述.     

酵母RNA聚合酶II羧基端结构域激酶CTDK-I及其亚基的结构与功能

RNA聚合酶Ⅱ最大亚基Rpb1的羧基端结构域（carboxyl-terminal repeat domain,CTD）是RNA聚合酶Ⅱ发挥转录延伸功能所必需的,对其执行精确的转录调节功能至关重要。酵母细胞周期蛋白依赖性激酶CTDK-I（carboxyl-terminal repeat domain kinase,CTDK-I）由CTK1、CTK2和CTK3组成,作用于RNA聚合酶Ⅱ羧基端结构域,动态磷酸化CTD的七肽重复序列（YSPTSPS）来调控转录和翻译。酵母中的特异性蛋白CTK3与特殊的细胞周期蛋白CTK2结合形成异二聚体,再与CTDK-I的催化亚基CTK1结合以调节其活性。CTK1作为细胞周期蛋白CDK（cyclin dependent kinase,CDK）的同源蛋白,其结构与功能的研究可拓展人们对CDK蛋白家族的认识;CTK2-CTK3复合物对CTK1调控机制的研究也可为细胞周期蛋白抑制剂的研发提供新的思路。本文简述了酵母CTDK-I的功能特点及其亚基的结构与功能以及亚基间的相互作用,并展望了CTDK-I复合物的研究前景。     

CTCF在介导三维基因组形成及调控基因表达中的研究进展

真核细胞间期的染色质在细胞核中经过复杂的盘曲折叠,形成高级拓扑结构,这样的染色质结构空间组织对基因表达有重要影响.CTCF(CCCTC-binding factor)作为关键的染色质高级结构架构蛋白,对三维基因组结构的形成起到了重要作用.CTCF还可以与基因组内大量的绝缘子结合,影响染色质远程交互,实现对增强子和基因转...     

hnRNP K的结构及功能

核内不均一性核糖核蛋白K（heterogeneous nuclear ribonucleoprotein K,hnRNP K）最早在hnRNA加工过程中被发现,属于hnRNP家族的一员。研究表明hnRNPK的主要功能结构为3个引导DNA—RNA连接的KH域和一个独特的KI域。hnRNP K不仅能够通过依赖CT元件的途径或不依赖CT元件的途径在转录水平上对基因表达进行调控,还能够通过自身的磷酸化,改变mRNA的翻译效率,以及调控基因翻译及转导胞内信号。此外,hnRNP K与肿瘤发生和转移的关系也是近年来的研究热点。hnRNP K被发现在许多肿瘤组织中高表达,主要通过调控与细胞增殖有关的基因表达而影响肿瘤的发生发展,同时它与肿瘤细胞的扩散转移也有关。     

锌指蛋白结构及功能研究进展

锌指蛋白是一类具有手指状结构域的转录因子,对基因调控起重要的作用。根据其保守结构域的不同,可将锌指蛋白主要分为C2H2型、C4型和C6型。锌指通过与靶分子DNA、RNA、DNA-RNA的序列特异性结合,以及与自身或其他锌指蛋白的结合,在转录和翻译水平上调控基因的表达。我们简要综述了近年来锌指蛋白结构、分类及其与核酸及蛋白质相互作用等方面的研究进展。     

植物MYB转录因子功能及调控机制研究进展

MYB转录因子是植物中数量最大、功能最多样的转录因子之一,在众多生命过程中扮演重要的角色,已成为当前植物基因功能及表达网络调控研究的热点。结合最新研究进展,综述了植物MYB转录因子家族的进化,并着重阐述了生物学功能及表达调控,为进一步分析功能未知的植物MYB转录因子提供参考。     

植物WRKY转录因子结构及功能研究进展

WRKY蛋白是植物所特有的转录因子家族.因WRKY结构域中的N-端均含有高度保守的WRJKYGQK氨基酸序列而得名.它能够与(T)TGACC(A/T)序列(W*box)发生特异性作用,调节启动子中含W-box元件的调节基因或功能基因的表达,从而参与植物的各种防卫反应,调节植物的发育和代谢等.近些年来.有关WRKY转录因子的研究很多,如模式生物中的拟南芥和水稻基因组中拥有大量的WRKY成员.主要介绍WRKY转录因子的结构特点及生物学功能.     

PIAS蛋白家族的研究进展

PIAS(protein inhibitor of activated STAT)蛋白家族是一种能够激活STAT转录活性的抑制蛋白,共包括4个成员,可与多种蛋白发生相互作用,从而影响靶蛋白的活性和功能,其主要与STAT、Wnt、TGF-β、NF-κB等通路的转录因子或转录辅因子相互作用以调控下游基因的转录活性。在细胞周期中,PIAS蛋白是细胞衰老和细胞凋亡的调节子,可促进细胞的扩散和衰老。在肿瘤发生中,PIAS蛋白的过表达能抑制癌细胞的增殖并诱导其凋亡。除此之外,在生殖系统和神经系统中,PIAS家族蛋白也能通过与相关的转录因子或激素受体相互作用影响其发生发展的过程。     

转录因子AKNA 功能调控的研究进展

转录因子AKNA是具有AT-hook模体的核内蛋白质,与富含AT碱基的DNA区域相结合调控靶基因的转录。AKNA主要在B淋巴细胞、T淋巴细胞、自然杀伤性细胞和干细胞上表达,介导免疫反应的发生。转录因子AKNA的单核苷酸多态性(SNP)可增加宫颈癌的风险,AKNA功能的丧失导致子宫颈肿瘤性病变。敲除AKNA基因可导致炎性因子、蛋白酶和趋化因子的富集,诱发中性粒细胞介导的炎性反应。本文从转录因子AKNA的结构特征、生物学功能和功能调控三方面进行综述,旨在为后续关于AKNA转录调控网络和信号通路的研究提供依据。     

细胞周期调控的研究进展

细胞周期是一种非常复杂和精细的调节过程,有大量调节蛋白参与其中。此过程的核心是细胞周期依赖性蛋白激酶（CDKs）。CDKs的激活又依赖于另一类呈细胞周期特异性或时相性表达的细胞周期蛋白（cyclins）,而CDKs调节的关键步骤是细胞周期检查点。PLKs是多种细胞周期检查点的主要调节因子,Aurora蛋白激酶主要在细胞有丝分裂期起作用。本文就上述因素在细胞周期进程中的作用作一综述。     

Condensin and cohesin knockouts in Arabidopsis exhibit a titan seed phenotype

The titan (ttn) mutants of Arabidopsis exhibit striking alterations in chromosome dynamics and cell division during seed development. Endosperm defects include aberrant mitoses and giant polyploid nuclei. Mutant embryos differ in cell size, morphology and viability, depending on the locus involved. Here we demonstrate that three TTN genes encode chromosome scaffold proteins of the condensin (SMC2) and cohesin (SMC1 and SMC3) classes. These proteins have been studied extensively in yeast and animal systems, where they modulate chromosome condensation, chromatid separation, and dosage compensation. Arabidopsis contains single copies of SMC1 and SMC3 cohesins. We used forward genetics to identify duplicate T-DNA insertions in each gene. These mutants (ttn7 and ttn8) have similar titan phenotypes: giant endosperm nuclei and arrested embryos with a few small cells. A single SMC2 knockout (ttn3) was identified and confirmed by molecular complementation. The weak embryo phenotype observed in this mutant may result from expression of a related gene (AtSMC2) with overlapping functions. Further analysis of titan mutants and the SMC gene family in Arabidopsis should provide clues to chromosome mechanics in plants and insights into the regulation of nuclear activity during endosperm development.     

Insights into the structural determinants of cohesin-dockerin specificity revealed by the crystal structure of the type II cohesin from Clostridium thermocellum SdbA

The plant cell wall degrading enzymes expressed by anaerobic microorganisms form large multienzyme complexes (cellulosomes). Cellulosomes assemble by the Type I dockerins on the catalytic subunits binding to the reiterated Type I cohesins in the molecular scaffold, while Type II dockerin-cohesin interactions anchor the complex onto the bacterial cell surface. Type I and Type II cohesin, dockerin pairs show no cross-specificity. Here we report the crystal structure of the Type II cohesin (CohII) from the Clostridium thermocellum cell surface anchoring protein SdbA. The protein domain contains nine beta-strands and a small alpha-helix. The beta-strands assemble into two elongated beta-sheets that display a typical jelly roll fold. The structure of CohII is very similar to Type I cohesins, and the dockerin binding site, which is centred at beta-strands 3, 5 and 6, is likely to be conserved in the two proteins. Subtle differences in the topology of the binding sites and a lack of sequence identity in the beta-strands that comprise the core of the dockerin binding site explain why Type I and Type II cohesins display such distinct specificities for their target dockerins.     

Interplay between CTCF boundaries and a super enhancer controls cohesin extrusion trajectories and gene expression

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Prophase pathway‐dependent removal of cohesin from human chromosomes requires opening of the Smc3–Scc1 gate

Faithful transmission of chromosomes during eukaryotic cell division requires sister chromatids to be paired from their generation in S phase until their separation in M phase. Cohesion is mediated by the cohesin complex, whose Smc1, Smc3 and Scc1 subunits form a tripartite ring that entraps both DNA double strands. Whereas centromeric cohesin is removed in late metaphase by Scc1 cleavage, metazoan cohesin at chromosome arms is displaced already in prophase by proteolysis‐independent signalling. Which of the three gates is triggered by the prophase pathway to open has remained enigmatic. Here, we show that displacement of human cohesin from early mitotic chromosomes requires dissociation of Smc3 from Scc1 but no opening of the other two gates. In contrast, loading of human cohesin onto chromatin in telophase occurs through the Smc1–Smc3 hinge. We propose that the use of differently regulated gates for loading and release facilitates unidirectionality of DNA's entry into and exit from the cohesin ring.     

染色体浓缩素

染色体的形成是细胞周期的重要事件,然而有关染色体构筑动力学的分子机制仍未阐明。近年来对染色体浓缩素的分离与研究,为认识DNA浓缩和染色体构建机制提供了重要的线索,是细胞生物学研究领域的里程碑。现对浓缩素的发现过程,浓缩素在有丝分裂和减数分裂中的作用,浓缩素与黏着素的关系,浓缩素参与基因调节等方面进行综述,为相关领域的研究者提供参考。     

Biology and insights into the role of cohesin protease separase in human malignancies

Separase, an enzyme that resolves sister chromatid cohesion during the metaphase‐to‐anaphase transition, plays a pivotal role in chromosomal segregation and cell division. Separase protein, encoded by the extra spindle pole bodies like 1 (ESPL1) gene, is overexpressed in numerous human cancers including breast, bone, brain, and prostate. Separase is oncogenic, and its overexpression is sufficient to induce mammary tumours in mice. Either acute or chronic overexpression of separase in mouse mammary glands leads to aneuploidy and tumorigenesis, and inhibition of separase enzymatic activity decreases the growth of human breast tumour xenografts in mice. This review focuses on the biology of and insights into the molecular mechanisms of separase as an oncogene, and its significance and implications for human cancers.     

人FAM33A基因启动子的克隆与鉴定

目的鉴定人FAM33A基因的启动子,为进一步研究其转录调控机制奠定基础。方法采用5’RACE技术（5’端cDNA快速扩增）鉴定FAM33A的转录起始位点。采用PCR定向克隆、酶切亚克隆等策略,构建FAM33A启动子荧光素酶报告基因。采用Lipofeetamine^TM2000转染H1299细胞,并通过Dual-Lu-ciferase@ Reporter Assay System进行荧光素酶报告基因活性检测。结果确定了FAM33A的转录起始位点,构建了覆盖FAM33A 5’端ATG附近约2kb区域的一系列FAM33A启动子荧光素酶报告基因。启动子活性分析表明,这些重组体均具有较高的启动子活性,同时含有典型的GC盒以及Sp1、E2F和GATA-1等潜在的转录因子结合位点。结论FAM33A启动子区域主要定位于转录起始位点附近约590bp的区域内。