哺乳類の内生転写と表遺伝子状態の光学制御
Silvana Konermann1,2, Mark D Brigham1,2,3, Alexandro Trevino1,2
1Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
Nature
|July 24, 2013
まとめ
研究者らは,哺乳類における遺伝子発現の精密な制御のための新しい光遺伝システムである光誘導トランスクリプションエフェクター (LITE) を開発した. この技術は,内生遺伝子の迅速で可逆的な調節と,内生遺伝子の改変を in vivo で可能にします.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- 神経科学は神経科学である.
背景:
- 遺伝子発現のダイナミクスは,細胞機能と適応に不可欠です.
- オプトジェネティックツールは精密な空間時間的な制御を提供するが,強固な哺乳類の転写調節には欠けている.
- 内生性哺乳類のゲノムを光学制御でターゲットにすることは,依然として課題です.
研究 の 目的:
- 哺乳類のシステムにおける内生的な遺伝子発現の精密な,光誘導制御のための汎用的な光遺傳システムを開発する.
- 光を用いた標的の表遺伝子改変を可能にする技術を開発する.
- 主要ニューロンにおけるシステムの有効性を検証し,自由行動するマウスの体内での有効性を検証する.
主な方法:
- TALEのDNA結合ドメインを暗号クローム2とCIB1.1と統合することで,光誘導型トランスクリプションエフェクター (LITE) を設計した.
- 青い光で活性化するカスタマイズ可能な2種類のハイブリッドシステムを開発しました.
- 特定の細胞集団の遺伝的標的化のためにウイルスのベクトルを利用した.
主要な成果:
- LITEは,外因的なコファクターなしで内生的な遺伝子発現の迅速 (数分) で可逆的な光学変調を可能にします.
- このシステムは,マウスのプライマリーニューロンと,生きているマウスの脳内の特定のゲノム位置を成功裏に標的とした.
- LITEシステムを使用した in vivo の標的型エピジェネティッククロマチンの改変が実証されました.
結論:
- LITEは,哺乳類の内生的な細胞プロセスを制御するための新しい光遺傳学的方法を提供します.
- このシステムは,生物学的プロセスや疾患における遺伝的および表遺伝的調節の直接的な調査を容易にする.
- LITEは,神経科学の研究と遺伝子機能の理解のための強力なツールです.
関連する概念動画
Epigenetic Regulation
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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...
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...


