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Epigenetic Regulation01:37

Epigenetic Regulation

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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...
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Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
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Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Regulation of Expression Occurs at Multiple Steps02:24

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Fto媒介 m6 エピジェネティック再プログラミングを調節することにより,小脳発育に必須である

Jing Jiang1, Ming Zhang1, Wenjuan Xia1

  • 1State Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou Centre), Suzhou Municipal Hospital, Gusu School, Suzhou Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Suzhou, 215002, China.

Journal of biomedical science
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PubMed
まとめ

マウスにおけるFto遺伝子の喪失は,表表表写体調節が変化したため,小脳アタクシアを引き起こした. この研究は,Fto

キーワード:
Fto についてカット8脳の発達H4K16ac についてキーワードm6A 変更

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科学分野:

  • 神経科学
  • エピジェネティクス
  • 分子生物学

背景:

  • エピトランスクリプトミックの調節,特にメチル化が,小脳発達と機能に不可欠である.
  • 小脳におけるRNAデメチラーゼFtoの特定の役割は不明である.

研究 の 目的:

  • マウスのノックアウトモデルを使用して小脳発達と機能におけるFtoの機能を調査する.
  • 小脳発達におけるFtoの役割に基づく分子メカニズムを解明する.

主な方法:

  • フェノタイプ分析のためにFtoノックアウト (FtoKO) マウスを生成した.
  • 行動検査とニッスル染色による小脳機能の評価
  • 免疫光,m6A-RIP-seq,ATAC-seq,CUT&Tag-seq,およびCo-IPを含む分子技術を使用して,遺伝子発現,m6Aレベル,およびクロマチンのアクセシビリティを分析した.

主要な成果:

  • FtoKOマウスは 震えと異常な歩行で脳小胞症を発症しました
  • FTO発現の減少はニューロンの発達と自己再生遺伝子の発現の変化につながった.
  • メカニズム的には,Ftoの損失は,Kat8のアップレギュレーション,m6Aレベルの増加,およびH4K16acの改変,クロマチンのアクセシビリティに影響を与えました.

結論:

  • Ftoは小脳発達において重要な役割を果たします.
  • Fto欠乏は,Kat8とクロマチンのアクセシビリティのA依存の調節によって小脳機能を乱します.
  • これらの発見は,神経発達過程における表表表記学的調節の重要性を強調しています.