Sp1元素は,CpG島をde novoメチル化から保護する

M Brandeis¹, D Frank, I Keshet

¹Department of Cellular Biochemistry, Hebrew University Medical School, Jerusalem, Israel.

Nature

|September 29, 1994

まとめ

Sp1要素は,初期胚形成の際に,家政遺伝子のCpG群島を新型甲基化から保護する. これにより,動物における遺伝子発現の調節に不可欠な正しいゲノムメチル化パターンが確保されます.

科学分野:

エピジェネティクスエピジェネティクス
発達生物学発達生物学について
ゲノミクスゲノミクスとは

背景:

動物の体細胞DNAは,バイモダルメチル化を示す:組織特異的な遺伝子はメチル化され,家政用遺伝子は非メチル化5'CpG島を持っています.
ゲメチルメチレーションは初期の胚では消去され,移植時にデノボメチル化によって,メチル化パターンが各世代ごとに再確立されることが必要になります.

研究の目的:

胚形成中にCpG島をde novoメチル化から保護するSp1元素の役割を調査する.
基底遺伝子調節のために正しいゲノムメチレーションパターンが確立されるメカニズムを解明する.

主な方法:

胚性幹細胞への転移を活用する.
遺伝子メチル化を研究するためのモデルシステムとして,トランス遺伝子マウスを採用.
アデニンフォスフォリボシルトランスフェラーゼ (APRT) 遺伝子のCpG島メチル化状態を分析する.

主要な成果:

Sp1要素は,APRT遺伝子のCpG島をデノボメチル化するのを防ぐ上で重要な役割を果たすことが示されました.
Sp1要素がCpG島を保護するための認識メカニズムとして機能することを実証しました.

結論:

Sp1元素は,初期開発において,CpG島をde novoメチル化から守る上で極めて重要です.
この保護機構は,正しい胚性ゲノムメチル化パターンの確立に不可欠であり,基礎遺伝子発現に影響を与えます.

さらに関連する動画

09:42

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images

Published on: September 7, 2017

07:50

Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina

Published on: August 29, 2018

関連する概念動画

01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.

02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...

02:40

The Eukaryotic Promoter Region

The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...

02:57

piRNA - Piwi-interacting RNAs

PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...

02:02

Cis-regulatory Sequences

01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...

関連する実験動画