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November 05, 2013


New Insights Into How Genes Turn On and Off Science dailyより


Researchers at UC Davis and the University of British Columbia have shed new light on methylation, a critical process that helps control how genes are expressed. Working with placentas, the team discovered that 37 percent of the placental genome has regions of lower methylation, called partially methylated domains (PMDs), in which gene expression is turned off. This differs from most human tissues, in which 70 percent of the genome is highly methylated.


While PMDs have been identified in cell lines, this is the first time they have been found in regular human tissue. In addition to enhancing our understanding of epigenetics, this work could influence cancer research and help illuminate how environmental toxins affect fetal development. The paper was published online this week in the Proceedings of the National Academy of Sciences (PNAS).


regular connective tissue定形結合組織
environmental toxins 環境毒素
fetal development 胎児発育

Since it was unraveled more than ten years ago, the human genome has been the focus of both popular interest and intense scientific focus. But the genome doesn't act alone; there are many factors that influence whether genes are turned on or off. One of these is an epigenetic process called methylation, in which a group of carbon and hydrogen atoms (a methyl group) attaches to DNA, adjusting how genes are expressed.


"I like to think of epigenetics as a layer on top of your genetic code," said senior author Janine LaSalle, professor of medical microbiology and immunology. "It's not the DNA sequence but it layers on top of that -- and methylation is the first layer. Those layers provide a lot of information to the cells on where and when to turn on the genes."

“私はあなたの遺伝子コード上に層としてエピジェネティックを考えるのが好きです。”と医学部微生物学免疫学の教授、第一著者Janine LaSalleは述べた。“それはDNA配列ではないが、それはDNA上の層である、メチル化は第一層である。これらの層はいつどこで遺伝子をオンにするかに関して細胞に多くの情報を提供します。

How and when genes are activated (or inactivated) can have a profound impact on human development, cancer and the biological legacy of environmental toxins. Prior to this research, PMDs had only been found in cultured cell lines, which led some scientists to wonder if they existed outside the test tube. This study confirms they exist in placental tissue, a critically important window into fetal development.


biological legacy 生物学的遺産
fetal development 胎児発育

"The placenta is the interface between mother and fetus," said LaSalle, who is a researcher affiliated with the UC Davis MIND Institute. "It's a time capsule from when a lot of important methylation events occurred."

“胎盤は母と胎児とのインターフェイスであると”、カリフォルニア大学デービス校のM.I.N.D. Institute所属のLaSalleは述べた。それは多くのメチル化が発生した時からのタイムカプセルだ。

Fetus 胎児 (人間では受胎後約 3 か月目からのもの)

In addition, placental tissue was interesting to study because it has a number of invasive characteristics often associated with cancer. In fact, a number of cancers, such as breast and colon, have widespread PMDs. LaSalle notes that anti-cancer epigenetic therapies that adjust methylation could be refined based on this improved understanding of PMDs.


invasive 浸潤

This work could also enhance our ability to detect genetic defects. Methylation, and other epigenetic data, provides information that cannot be found in the genome alone. For example, the vast majority of cells in the body contain identical genetic code. However, the added information provided by methylation allows scientists to determine where specific DNA came from.
また、この研究は遺伝子異常の検出力を増強することが出来るだろう。メチル化、および他のエピジェネティック データは、ゲノム単独で見つけることの出来ない情報を提供する。例えば、
大部分の体内細胞は同一の遺伝子コードを含んでいる。 しかし、メチル化によって付加された追加情報は特異的DNAがどこから来たかを科学者に決定させます。

"Methylation patterns are like fingerprints, showing which tissue that DNA is derived from," LaSalle said. "You can't get that information from just the DNA sequence. As a result, methylation studies could be a very rich source for biomarkers."


In the study, PMDs encompassed 37 percent of the placental genome, including 3,815 genes, around 17 percent of all genes. When found in low-methylation regions, these genes were less likely to be transcribed into proteins. Researchers also found that PMDs also contain more highly methylated CpG islands (genomic areas with large numbers of cytosine-guanine pairs), which are often associated with gene transcriptional silencing of promoters.


cytosine-guanine pairs シトシン‐グアニン塩基対

Because the placental PMDs contained many genes associated with neuronal development, and specifically autism, LaSalle notes that future research could investigate how epigenetics impacts autism genes at birth.


"We are looking for biomarkers that predict neurodevelopmental outcomes," LaSalle said. "Now we have a series of snap shots from a critical period where we think environmental factors are playing a role in the developing brain."

"私たちは、神経発達の転帰を予測するバイオマーカーを探していますと、 " LaSalleラサールは述べた。 "今、私たちは環境因子が脳の発達に役割を果たしている時期からの一連のスナップショットを持っています。

neurodevelopmental outcomes 神経発達の転帰




DNAメチル化は遺伝子転写の重要な調節装置であり、異常なDNAメチル化が予定外の遺伝子サイレンシングと関連していること、プロモーター領域に高いレベルの5-メチルシトシン(英語版)を含む遺伝子は転写が休止していることが、多くの証拠から明らかにされている。DNAメチル化は、胚の発達に必須であり、体細胞ではDNAメチル化の様式は一般的に高い忠実性を持って娘細胞に受け継がれる。異常DNAメチル化様式は、多くのヒト悪性腫瘍と関連しており正常組織と比較して過剰メチル化と低メチル化の2つの異なる形がある。過剰メチル化は、がん抑制遺伝子のプロモーター領域に作用し転写を抑制する主要なエピジェネティク修飾の1つである。過剰メチル化は通常プロモーター領域のCpGアイランドで起こり、遺伝子の不活性化と関連している。広範囲な低メチル化もまた、異なる機構でのがんの発達および悪性化と関連している[12]。 遺伝子プロモーター領域のメチル化による遺伝子不活化の例として、ヒト乳癌、子宮癌におけるエストロジェン受容体欠如、非遺伝性乳癌におけるBRCA1の不活性化をあげることができる。


遺伝子サイレンシング(英:gene silencing、遺伝子抑制、ジーンサイレンシング)[1]とは一般に、クロマチンへの後天的な修飾により遺伝子を制御する、いわゆるエピジェネティクス的遺伝子制御のことを示す[2]。









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