英语文献信度与评价分析.docxVIP

文献阅读+信度与权威分析生命学院D201577459 林生彦《Large conserved domains of low DNA methylation maintained by Dnmt3a》Summary：Gains and losses in DNA methylation are prominent features of mammalian cell types. To gain insight into the mechanisms that promote shifts in DNA methylation and contribute to changes in cell fate, including malignant transformation, we performed genome-wide mapping of 5-methylcytosine and 5-hydroxymethylcytosine in purified mouse hematopoietic stem cells. We discovered extended regions of low methylation (canyons) that span conserved domains frequently containing transcription factors and are distinct from CpG islands and shores. About half of the genes in these methylation canyons are coated with repressive histone marks, whereas the remainder are covered by activating histone marks and are highly expressed in hematopoietic stem cells (HSCs). Canyon borders are demarked by 5-hydroxymethylcytosine and become eroded in the absence of DNA methyltransferase 3a (Dnmt3a). Genesdysregulated in human leukemias are enriched for canyon-associated genes. The new epigenetic landscape we describe may provide a mechanism for the regulation of hematopoiesis and may contribute to leukemia development.摘要：（中文）DNA甲基化的积累和丢失是哺乳动物细胞中显著存在的特征。为了深刻解析促进DNA甲基化的发生以及导致细胞命运变化的机制（包括恶性转化），我们在纯净的小鼠造血细胞中进行了5-甲基胞嘧啶以及5-羟甲基胞嘧啶全基因组比对。我们发现，低甲基化部分的延伸区跨越了转录因子频率较高的保守结构域，而这个区域与CpG岛是截然不同的。在这个甲基化延伸区，将近一半的基因表面含有具有抑制作用的组蛋白标记，而剩余部位则被具有活性的组蛋白标记覆盖，并且在造血细胞（HSCs）中高表达。（低甲基化部分）延伸区边缘被5-羟甲基胞嘧啶分隔开，并且在DNA甲基转移酶3a（Dnmt3a）缺乏的情况下被侵蚀掉。在人类白血病中，基因的调节异常丰富了（低甲基化部分）延伸区边缘的基因。我们描述的这个新表观遗传现象也许能为造血作用的调节作用提供一种机制，并可能对白血病的发展有贡献。《The R882H DNMT3A Mutation Associated with AML Dominantly Inhibits Wild-Type DNMT3Aby Blocking Its Ability to Form Active Tetramers》Summary：Somatic mutations in DNMT3A, which encodes a de novo DNA methyltransferase, are found in 30% of normal karyotype acute myeloid leukemia (AML) cases. Most mutations are heterozygous and alter R882 within the catalytic domain (most commonly R882H), suggesting the possibili