在KMT2A重新排列的急性淋巴细胞白血病中,染色质和异常增强剂活性
1MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
Current opinion in genetics & development
|April 5, 2024
概括
基因增强剂对于发育至关重要,但它们的功能尚不清楚. 混合血统白血病 (MLL或KMT2A) 在白血病中的重组驱动异常增强剂活性,提供对基因调节和疾病的见解.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 多细胞发育依赖于精确的基因转录.
- DNA增强剂在发育过程中调节基因表达.
- 增强剂活性的确切机制尚未完全理解.
研究的目的:
- 调查混合血统白血病 (MLL或KMT2A) 重组在异常增强剂活性中的作用.
- 了解MLL-AF4融合蛋白对驱动基因表达的复杂组件的依赖.
- 提供有关MLLR的增强器功能和转录异质性的见解.
主要方法:
- 分析MLL-AF4融合蛋白在驱动增强剂活性中的作用.
- 调查对MLL-AF4复杂组件的依赖性.
- 观察MLLR患者的转录模式.
主要成果:
- 在急性淋巴细胞白血病 (ALL) 中,MLL-AF4融合蛋白驱动了急性淋巴细胞白血病 (ALL) 中关键瘤基因的异常增强活性.
- 这种异常活动取决于MLL-AF4复杂组件的持续存在.
- 观察提供了对一般增强器功能的见解.
结论:
- 在白血病中,MLL重组有助于异常增强剂活性.
- 了解这些机制可以解释MLLR患者的转录异质性.
- 这项研究揭示了基因调节和潜在的治疗点.
更多相关视频
09:52A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
Published on: December 4, 2018
7.5K
10:41An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
10.4K
相关概念视频
Spreading of Chromatin Modifications
8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.3K
Chromatin Position Affects Gene Expression
23.3K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
23.3K
Chromatin Modification in iPS Cells
1.6K
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...
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...
1.6K
Histone Modification
13.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Epigenetic Regulation
3.0K
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...
3.0K
