热力学原理将体外转录因子亲缘关系与细胞中的单分子染色体状态联系起来
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在PubMed上查看摘要
概括
此摘要是机器生成的。这项研究揭示了DNA序列环境如何影响转录因子 (TF) 的结合和染色质的可访问性. 对红细胞克鲁佩尔样因子 (eKLF/KLF1) 结合的生物物理见解预测了体内TF行为.
科学领域
- 分子生物学
- 基因组学
- 生物物理
背景情况
- 对转录因子 (TF) 结合和染色质可访问性的定量理解仍然不完整.
- 关键问题包括序列上下文如何影响TF亲和力,DNA搜索机制,占用动力学和动机语法协调.
研究的目的
- 通过使用人类红色素克鲁佩尔样因子 (eKLF/KLF1) 来定量阐明TF结合和染色质可访问性的分子机制.
- 将体外生物物理测量与体内单分子观测和深度学习模型进行比较.
主要方法
- 高通量体外TF结合率和亲和度测试.
- 在体内测量单分子TF和核细胞占用率.
- 使用体内数据进行深度学习模型开发.
主要成果
- 附带DNA序列显著调节TF亲和力,影响TF搜索参数,与线性能量模型一致.
- 动机识别概率,而不是绑定时间,决定了亲和力变化.
- 在实验室和细胞核中观察到一致的TF停留时间 (分钟).
- 试验室生物物理参数成功预测了新型基因语法中的体内序列偏好和染色质状态.
结论
- 这项研究为了解TF-DNA相互作用和染色体调节提供了定量框架.
- 试管生物物理测量可以预测体内TF行为,提供对基因调节的见解.
相关概念视频
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...
Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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...
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...
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...