福克斯A1将表观遗传特征转化为增强器驱动的谱系特异转录
Mathieu Lupien1, Jérôme Eeckhoute, Clifford A Meyer
1Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Cell
|March 25, 2008
概括
结合DNA的FoxA1先驱因子建立了细胞特异性基因程序. 它对染色质的招募取决于基因素甲基化,指导增强剂的形成和细胞身份.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组学就是基因组学.
背景情况:
- 复杂的生物体需要组织特异性的基因表达来进行发育和功能.
- 转录因子FoxA1是已知的先驱因子,能够与核细胞体内的DNA结合.
- 了解FoxA1如何建立细胞特异性功能对于发育生物学至关重要.
研究的目的:
- 研究FoxA1细胞类型特异性功能背后的机制.
- 确定FoxA1如何与染色质和其他因素相互作用以调节基因转录.
- 确定指导FoxA1招募到特定基因组位置的表观遗传线索.
主要方法:
- 用全基因组定位分析绘制了FoxA1结合部位的地图.
- 与FoxA1结合相关的染色体结构变化被评估.
- 研究了基因组修饰的作用,特别是基因组H3 lysine 4二甲基化.
主要成果:
- 福克斯A1的细胞特异性作用主要是由它对远程增强剂的招募驱动的,而不是近距离促进剂.
- 不同的FoxA1招募改变了染色质结构,并促进了与谱系特定的转录因子的协作.
- 福克斯A1的差异性染色质结合取决于素H3 lysine4二甲基化存在.
结论:
- 基因组H3氨酸4二甲基化作为FoxA1招募的表观遗传特征.
- 福克斯A1利用这种表观遗传特征来修改染色质结构,建立血统特定的增强剂和转录程序.
- 这项研究阐明了产生细胞类型特定基因表达模式的关键机制.
相关概念视频
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02:16Transcription Factors
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...
02:16Transcription Factors
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...
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
01:30General Transcription Factors
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...
01:37Epigenetic 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...