SLAM-seqはBRD4-MYC軸の直接的な遺伝子調節機能を定義する
Matthias Muhar1, Anja Ebert1, Tobias Neumann1
1Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), 1030 Vienna, Austria.
Science (New York, N.Y.)
|April 7, 2018
まとめ
研究者はSLAM-seqを使用して,がんに関連する遺伝子BRD4とMYCの直接標的を特定しました. BET阻害剤はBRD4を広く抑制したが,選択的にMYCを活性化させ,がんにおける明確な役割と標的の特定のための新しい戦略を明らかにした.
科学分野:
- 分子生物学
- 癌 研究
- ゲノミクス
背景:
- 生理学と病気における転写因子の役割を理解するには,直接的な分子標的を定義する必要があります.
- BRD4とMYCは,がんの発生と進行に関与する重要な転写ハブです.
研究 の 目的:
- BRD4とMYCの規制機能を定義する.
- BRD4とMYCの直接的な転写標的を特定する.
- BETブロモドメイン阻害剤 (BETis) に対する直接反応を調査する.
主な方法:
- 新しく合成されたmRNAの直接定量化のための結合SLAM-seq (RNAの代謝シーケンシング).
- 薬理学的および化学的遺伝的干渉戦略
- BRD4とMYCによる転写調節の分析
主要な成果:
- BRD4はRNAポリメラーゼII転写の一般的同活性化剤として機能し,高用量BETによって広く抑制される.
- BETは,MYCを含む過敏標的のサブセットを,白血病に関連する治療用量で選択的に緩和します.
- MYCは選択的転写活性化剤として作用し,主にリボソーム生物生成や purin合成などの代謝プロセスを制御する.
結論:
- BRD4とMYCは,BET阻害剤に対する異なった転写作用と反応を示す.
- SLAM-seqは,混乱と組み合わせて,直接の転写標的を特定するためのスケーラブルな戦略を提供します.
- このアプローチは,様々な生物学的文脈で遺伝子と経路の機能を明らかにすることができます.
さらに関連する動画
10:10Retroviral Scanning: Mapping MLV Integration Sites to Define Cell-specific Regulatory Regions
Published on: May 28, 2017
8.9K
13:48Discovering CsgD Regulatory Targets in Salmonella Biofilm Using Chromatin Immunoprecipitation and High-Throughput Sequencing ChIP-seq
Published on: January 18, 2020
8.1K
関連する概念動画
01:28Piecewise-Defined Functions
310
Piecewise defined functions are mathematical models where different expressions define a function over distinct intervals of the domain. These functions are useful for representing systems with varying behaviors depending on input values.For example, the function: uses a linear rule for inputs less than or equal to –1 and a quadratic rule for values greater than –1. Although it has two formulas, it still defines a single function.Another common type is the absolute value...
310
01:29Rules for Defining Functions
384
A relation is a function if each input x is associated with exactly one output y. For example, the equation y = 2x + 5 defines a function because every value of x yields a unique y. However, x = y² + 1 is not a function of x, since a single x-value, such as x = 2, corresponds to two possible y-values: y = 1 and y = -1.The vertical line test helps determine whether a graph represents a function. If a vertical line intersects a curve more than once, the curve fails...
384
02:02Cis-regulatory Sequences
11.9K
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...
11.9K
02:33Combinatorial Gene Control
9.7K
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...
9.7K
01:37Hypothalamic-Pituitary Axis
66.5K
The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
66.5K
01:42What is Gene Expression?
197.0K
Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
197.0K