DNA甲基转移酶的表达调控及主要生物学功能

DNA甲基化是表观遗传学的重要部分, 同组蛋白修饰相互作用, 通过改变染色质结构, 调控基因表达。在哺乳类细胞或人体细胞中, DNA甲基化与细胞的增殖、衰老、癌变等生命现象有着重大关系。对催化DNA甲基化的DNA甲基转移酶(DNA methyltransferase, Dnmt)的研究可以揭示DNA甲基化对基因表达调控的机制, 从而研究与之相关的重要生命活动。文章以DNA甲基转移酶作为切入点, 探讨DNA甲基转移酶在基因表达调控中发挥的作用及其主要生物学功能。     

A “GC-rich” method for mammalian gene expression:A dominant role of non-coding DNA GC content in the regulation of mammalian gene expression

High mammalian gene expression was obtained for more than twenty different proteins in different cell types by just a few laboratory scale stable gene transfections for each protein.The stable expression vectors were constructed by inserting a naturally-occurring 1.006 kb or a synthetic 0.733 kb DNA fragment(including intron) of extremely GC-rich at the 5' or/and 3' flanking regions of these protein genes or their gene promoters.This experiment is the first experimental evidence showing that a non-coding ex...     

A physiological role for DNA supercoiling in the anaerobic regulation of colicin gene expression

Summary The mechanism of anaerobic regulation of synthesis of colicins E1, E2, E3, K and D was studied. It was found that anaerobiosis significantly increases expression of the genes for colicins E1, E2, E3, K, and D. Experiments with novobiocin (a DNA gyrase inhibitor) showed that colicin synthesis in minicells and derepressed colicin synthesis in cells are dramatically reduced by relaxation of DNA supercoiling. A good correlation was observed between the levels of colicin synthesis and plasmid DNA supercoiling and the degree of aeration of the cultures. Thus, the regulation of colicin gene expression in response to a change in aeration appears to be mediated by environmentally induced variations in DNA supercoiling.     

Sirt基因家族及其对细胞寿命的调节

在酵母、线虫和果蝇中,Sir2基因家族是寿命调节的关键因子。哺乳动物的Sirt基因家族在进化上与Sir2基因高度同源,共有7个成员。Sir2基因调节酵母寿命的机理已比较清楚。而哺乳动物Sirt基因,特别是Sirt1基因与细胞衰老的关系正在成为新的研究热点。最近的研究表明,在热量限制或氧化逆境条件下,SIRT1蛋白主要是通过以下3个途径影响细胞寿命:一是SIRT1蛋白抑制PPAR-γ减少细胞的脂质过氧化的损伤;二是SIRT1蛋白通过调控p53的活性影响细胞寿命;三是SIRT1蛋白通过调控FOXO的信号通路,启动细胞的抗氧化途径。进一步研究Sirt基因家族对揭示哺乳动物寿命之谜具有重要的科学意义。     

The role of microRNA in the delayed negative feedback regulation of gene expression

Oscillatory gene expression plays an important role in somite segmentation during the early developmental stages of vertebrates. Recent experimental studies have shown that microRNA can regulate gene expression by stimulating degradation of mRNA and/or repression of translation. In this communication, we incorporate miRNA into a previous mathematical model of gene expression with delayed negative feedback and demonstrate how this modified model can elucidate the possible effect of miRNA on the oscillatory gene expression. Our finding suggests that miRNA maybe a destabilizing or stabilizing factor in the dynamics of gene expression depending on the severity of its effect on mRNA degradation. Our finding provides testable hypothesis for experimental biologists to further investigate miRNA's increasing functional roles in regulating cellular processes and development.     

The role of the sporulation gene spollIE in the regulation of prespore-specific gene expression in Bacillus subtilis

The spoIIIG gene encodes a sigma factor that determines prespore-specific gene expression during sporulation in Bacillus subtilis. Correct spatial and temporal expression of the spoIIIG gene depends on a number of other sporulation (spo) genes, but only one of these genes, spoIIIE, has a specific effect on spoIIIG expression and not on gene expression in the other differentiating cell, the mother cell. However, the spoIIIE gene is expressed predominantly before differentiation begins. Thus, its product must play an important role in sensing or determining the spatial localization of prespore-specific gene expression in this system.     

DNA methyltransferases control telomere length and telomere recombination in mammalian cells

Here, we describe a role for mammalian DNA methyltransferases (DNMTs) in telomere length control. Mouse embryonic stem (ES) cells genetically deficient for DNMT1, or both DNMT3a and DNMT3b have dramatically elongated telomeres compared with wild-type controls. Mammalian telomere repeats (TTAGGG) lack the canonical CpG methylation site. However, we demonstrate that mouse subtelomeric regions are heavily methylated, and that this modification is decreased in DNMT-deficient cells. We show that other heterochromatic marks, such as histone 3 Lys 9 (H3K9) and histone 4 Lys 20 (H4K20) trimethylation, remain at both subtelomeric and telomeric regions in these cells. Lack of DNMTs also resulted in increased telomeric recombination as indicated by sister-chromatid exchanges involving telomeric sequences, and by the presence of 'alternative lengthening of telomeres' (ALT)-associated promyelocytic leukaemia (PML) bodies (APBs). This increased telomeric recombination may lead to telomere-length changes, although our results do not exclude a potential involvement of telomerase and telomere-binding proteins in the aberrant telomere elongation observed in DNMT-deficient cells. Together, these results demonstrate a previously unappreciated role for DNA methylation in maintaining telomere integrity.