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表观遗产学上的一些基因选择不表征的原因

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发表于 2011-12-5 00:39:41 | 显示全部楼层 |阅读模式
Japanese and U.S. scientists in the young field of epigenetics have reported a rationale as to how specific genes are silenced and others are not. Because this effect can be reversed, it may be possible to devise therapies for cancer and other diseases using this information.
The NOVA U.S. public television program described epigenetics as "The Ghost In Your Genes." It is the study of changes in gene expression that occur without changes in dna sequence. Like keys on a piano, DNA is the static blueprint for all the proteins that cells produce. Epigenetic information provides additional dynamic or flexible instructions as to how, where and when the blueprint will be used. "It corresponds to a pianist playing a piece of music," said Kohzoh Mitsuya, Ph.D., postdoctoral fellow in the School of Medicine at The University of Texas Health Science Center San Antonio.


Dr. Kohzoh Mitsuya



Article in Science
The study by Dr. Mitsuya and colleagues is outlined in the May 13 issue of the journal Science. The team found that a small RNA pathway is required to establish an epigenetic modification -- called DNA methylation -- at a gene that codes for mammalian proteins. DNA methylation adds chemical tags called methyl groups to specific genes, usually silencing their expression.


"DNA methylation marks are reversible, so there is great interest in devising therapeutic strategies, for instance in cancer biology, to epigenetically reactivate silenced tumor-suppressor genes or inactivate specific oncogenes in human cancer cells," Dr. Mitsuya, the Science paper's third author, said. The lead author is Toshiaki Watanabe, Ph.D., of the National Institute of Genetics in Japan and Yale University.


Environment and cancer


Beyond being reversible, DNA methylation is susceptible to environmental influences. Many cancer biologists now agree that changes in DNA methylation might be as important as genetic mutations in causing cancer. There are far more epigenetic changes than genetic changes found in the majority of cancers, and research into epigenetics is proving to be important to understanding cancer biology.


"It is critical to identify the entire complement of factors that affect gene silencing," Dr. Mitsuya said. "This was the rationale behind this study examining DNA methylation in mice that I began in 2004. The study adds information about one set of factors."


A finger on the piano

The researchers compared a group of normal mice with a group lacking the small RNA species. The team found that DNA methylation was markedly reduced at one of four genes tested in the small RNA-deficient mice. "This is the first demonstration that small RNAs can act in this way," Dr. Mitsuya said. "It shows how one note is played on the piano."


Epigenetic activity is a previously unseen dimension of biology that may enable clearer detection of disease, monitoring of progression and improved treatment, and may provide entirely new biomarkers of disease susceptibility. "The symphony has only just come into view," Dr. Mitsuya said. "We can hear it, but we need to learn how all the parts are being played."


Dr. Mitsuya is a member of the Center for Pregnancy and Newborn Research in the Department of Obstetrics and Gynecology, School of Medicine, at the UT Health Science Center San Antonio and is engaged in epigenetic studies of placental function.



日本和美国青年在表观遗传学领域的科学家曾报道一个特定的基因是如何保持沉默的理由和别人不。因为这种效果可以逆转的,它可能会制订使用此信息治疗癌症和其他疾病的治疗。

新星美国公共电视节目形容为表观遗传学“鬼在你的基因。”它是研究DNA序列的变化,没有发生基因表达的变化。就像钢琴上的键,DNA是所有细胞产生的蛋白质,静态的蓝图。表观遗传信息如何,何时何地的蓝图将被用来提供额外的动态或灵活的指示。 “它相当于一个钢琴家演奏一首乐曲,Kohzoh三矢,博士,在得克萨斯大学健康科学中心圣安东尼奥大学医学院博士后研究员说。”

Dr. Kohzoh Mitsuya

“科学”上的文章

三矢博士和他的同事的研究概述在5月13日的“科学”杂志上的问题。该研究小组发现,小RNA途径是建立了一种基因,表观遗传修饰 - 所谓的DNA甲基化 - 哺乳动物蛋白的代码。 DNA甲基化增加了所谓的特定基因的甲基组的化学标记,平时沉默的表达。
“DNA甲基化标志是可逆的,所以在制订治疗策略有极大的兴趣,例如在癌症生物学,表观遗传学激活沉默的抑癌基因或灭活特定的致癌基因,在人类癌细胞中,”三矢,博士科学论文的第三作者说。主要作者是渡边敏明,博士,在日本和美国耶鲁大学遗传学研究所。

环境与癌症

除了DNA甲基化是可逆的,容易受到环境的影响。现在,许多癌症生物学家同意,在DNA甲基化的变化可能会引起癌症的基因突变的重要。有更多的后生变化远远比大多数癌症发现的遗传变化,到表观遗传学的研究被证明是了解癌症生物学的重要。

“这是关键,以确定基因沉默的因素会影响整个补充,三矢博士说。” “这是理由的背后,我于2004年开始研究在小鼠体内的DNA甲基化的研究。,这项研究增加了约一因素的信息。”

钢琴上的手指

研究人员比较了一组正常小鼠与缺乏小分子RNA的物种。该研究小组发现,DNA甲基化的显着减少在小RNA基因缺陷小鼠测试的四个基因之一。 “这是首次证明了小分子RNA可以在这种方式行事,”三矢博士说。 “这表明,一个值得注意的是如何在钢琴上演奏。”

后生活动是以前看不到的生物学的层面可能使更清晰的疾病检测,监测进展和改进治疗,完全可以提供新的生物标志物的疾病易感性。 “交响乐才刚​​刚映入眼帘,”三矢博士说。 “我们可以听到它,但我们需要学习如何正在播放的所有部件。”
三津博士是妇产科医学院部妊娠和新生儿研究中心的成员,在得克萨斯大学健康科学中心圣安东尼奥和从事在胎盘功能的后生研究。
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