通过染色体阅读器SGF29进行白血病发生的转录控制
Karina Barbosa1, Anagha Deshpande1, Marlenne Perales1
1Cancer Genome and Epigenetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA.
Blood
|December 4, 2023
概括
研究人员确定SGF29是急性髓性白血病 (AML) 的新型依赖. 针对SGF29Tudor域可能为AML患者提供新的治疗策略,影响白血病干细胞存活率.
科学领域:
- 血液学 血液学 血液学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 异常干细胞基因表达驱动急性髓性白血病 (AML) 的自我更新和抵抗.
- 在AML中,AF10重排列的白血病是AML中激活的"干"网络的例子.
- 白血病干细胞 (LSCs) 对AML的维持和复发至关重要.
研究的目的:
- 确定维持AML中的"茎"网络的染色体调节剂.
- 研究Tudor域蛋白SGF29在AML癌基因转录中的作用.
- 探索SGF29作为一个潜在的治疗点在AML.
主要方法:
- 使用以域为中心的库进行CRISPR-Cas9选.
- 使用CRISPR滴滴测序来分析基因调节.
- 在AML模型中进行功能性研究,以评估白血病发生.
主要成果:
- 确定了调节MEIS1,一个关键的LSC基因的新型染色质修饰复合体.
- 鉴定出SGF29是AML瘤基因转录的一个新型调节剂.
- 在多种AML亚型中,SGF29删除损害了白血病发生.
- SGF29 Tudor域名成为潜在的毒品目标.
结论:
- 在AML的进展中,SGF29起着关键的非致癌作用.
- 准SGF29为AML提供了一个有前途的治疗策略.
- SGF29Tudor域是AML药物发现的新目标.
更多相关视频
相关概念视频
Combinatorial Gene Control
8.4K
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...
8.4K
General Transcription Factors
5.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.3K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
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
Transcription Factors
75.9K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
75.9K
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


