Antagonism between DNA hypermethylation and enhancer-blocking activity at the H19 DMD is uncovered by CpG mutations

Imprinted expression at the H19-Igf2 locus depends on a differentially methylated domain (DMD) that acts both as a maternal-specific, methylation-sensitive insulator and as a paternal-specific site of hypermethylation. Four repeats in the DMD bind CCCTC-binding factor (CTCF) on the maternal allele and have been proposed to attract methylation on the paternal allele. We introduced point mutations into the DMD to deplete the repeats of CpGs while retaining CTCF-binding and enhancer-blocking activity. Maternal inheritance of the mutations left H19 expression and Igf2 imprinting intact, consistent with the idea that the DMD acts as an insulator. Conversely, paternal inheritance of these mutations disrupted maintenance of DMD methylation, resulting in biallelic H19 expression. Furthermore, an insulator was established on the paternally inherited mutated allele in vivo, reducing Igf2 expression and resulting in a 40% reduction in size of newborn offspring. Thus, the nine CpG mutations in the DMD showed that the two parental-specific roles of the H19 DMD, methylation maintenance and insulator assembly, are antagonistic.     

Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity

Legionella pneumophila, the causative agent of Legionnaires' disease, replicates as an intracellular parasite of amoebae and persists in the environment as a free-living microbe. Here we have analyzed the complete genome sequences of L. pneumophila Paris (3,503,610 bp, 3,077 genes), an endemic strain that is predominant in France, and Lens (3,345,687 bp, 2,932 genes), an epidemic strain responsible for a major outbreak of disease in France. The L. pneumophila genomes show marked plasticity, with three different plasmids and with about 13% of the sequence differing between the two strains. Only strain Paris contains a type V secretion system, and its Lvh type IV secretion system is encoded by a 36-kb region that is either carried on a multicopy plasmid or integrated into the chromosome. Genetic mobility may enhance the versatility of L. pneumophila. Numerous genes encode eukaryotic-like proteins or motifs that are predicted to modulate host cell functions to the pathogen's advantage. The genome thus reflects the history and lifestyle of L. pneumophila, a human pathogen of macrophages that coevolved with fresh-water amoebae.     

Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B

Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses. In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, we identified truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint. These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development.     

深圳福田红树林区浮游藻类时空分布的研究

在2005年11月(秋)、2006年1月(冬)、2006年4月(春),分别对深圳福田红树林保护区5个水质监测站的浮游藻类进行采样研究.共鉴定到浮游藻类5门27属52种(含1变种和9未知种),密度在1.2×106～8.8×106个/L之间,平均密度为4.9×106个/L.硅藻门种类最多,有17属35种(含未知7种),占总种类数的67.3%,而且密度最大,高达8.7×106个/L;最少为隐藻门的种类,尚未发现甲藻门的种类.耐污染特征的种类如极微小环藻(Cyclotella caspia)、颤藻(Oscillatoria spp.)和小球藻(Chlorella vulgaris)是藻类群落的主要成分.各站分布的藻类群落组成季节差异明显,而种类数和密度并没有明显的季节变化.各站的优势种和优势类群存在时空差异.评价各站水质,反映出该红树林区水体处在中营养至富营养化状态.     

癌生长是寄主中的过寄生现象

报道了人乳腺癌细胞MCF7和正常细胞MCF10,MRC5混合培养实验,分析了实验结果．结果表明：在营养物充足条件下癌细胞和正常细胞系寄生共存关系,而在饥饿条件下癌细胞和正常细胞是过寄生-捕食者和食饵的关系．讨论了此结果的生物医学含义．