初期の哺乳類の胚におけるDNAメチレーションのユニークな規制段階である
Zachary D Smith1, Michelle M Chan, Tarjei S Mikkelsen
1Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Nature
|March 30, 2012
まとめ
哺乳類の胚形成には,DNAのメチル化が動的に変化する. 新しい塩基解像度マップは,初期の胚で維持される卵細胞由来メチル化パターンを明らかにし,既存のモデルに挑戦しています.
科学分野:
- エピジェネティクスと発達生物学
- ゲノミクスとバイオインフォマティクス
背景:
- 哺乳類の胚形成は,発達に不可欠なダイナミックなDNAメチル化が特徴である.
- 既にある父親のゲノム脱メチル化のモデルは,限られたデータに基づいている.
- 初期胚形成におけるDNAメチル化に関するベース解像度の地図は存在しない.
研究 の 目的:
- ゲノムスケール,塩基解像度のDNAメチル化マップをマウスゲメタおよび初期の胚で生成する.
- 哺乳類の植入前の発達過程におけるDNAメチル化ダイナミクスの理解を深める.
- 卵細胞と精子によって寄与されるユニークなメチル化パターンを特定する.
主な方法:
- マウスの精子,卵細胞,卵胞,移植後の胚の全ゲノムバイスルファイト配列解析 (Whole-genome bisulfite sequencing,WGBS) を実施した.
- ベース解像度のDNAメチレーションマップを生成するためのバイオ情報分析.
- 微分メチル化領域 (DMR) の識別と特徴付け.
主要な成果:
- 卵子細胞は,特に特定のレトロエレメントにおいて,全局的な低メチル化を示し,精子より低ジゴティックメチル化を示します.
- 卵細胞は,CpG島プロモーターを含むユニークなDMRを寄与し,初期の胚で維持され,体細胞で失われます.
- 精子によって寄与されるDMRは,主にインタージェニックであり,高メチル化したプラストキスト後期となる.
結論:
- 初期の哺乳類の胚におけるDNAメチル化ダイナミクスの包括的なベース解像度タイムラインを提供します.
- 発達初期に一時的な新しい卵細胞由来メチル化パターンを明らかにします.
- 哺乳類の胚形成における全ゲノムデメチル化と再プログラムに関する既存のモデルに挑戦し,精製する.
関連する概念動画
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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...
X-chromosome...
Genomic Imprinting and Inheritance
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
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Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
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After a large-single-celled zygote is produced via fertilization, the process of cleavage occurs while zygotes travel through the uterine tube. Cleavage is a mitotic cell division that does not result in growth. With each round of successive cell division, daughter cells get increasingly smaller.
Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...


