广泛存在的低亲和度图案增强了mESCs中的染色质可访问性和监管潜力
Melanie Weilert1, Kaelan J Brennan1, Khyati Dalal1,2
1Stowers Institute for Medical Research, Kansas City, MO, USA.
bioRxiv : the preprint server for biology
|December 3, 2025
概括
低亲和度转录因子 (TF) 动机对于基因调节至关重要,但很难绘制地图. 这项研究揭示了它们通过核细胞相互作用进行合作,增强它们的调控潜力和微调发育增强剂.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 低亲和度转录因子 (TF) 动机是cis-regulatory代码的关键组成部分.
- 它们的映射和机械理解仍然具有挑战性,阻碍了对发展,进化和疾病中非编码变异的解释.
研究的目的:
- 调查低亲和度TF图案在开拓性中的作用.
- 以可靠地绘制和解释这些基因组在整个基因组使用序列到配置文件的染色质可访问性模型.
主要方法:
- 在小鼠胚胎干细胞中利用了染色质可访问性的序列到配置文件模型.
- 开发了一种动力模型来分析核细胞介导的合作性.
- 研究了用于动机合作的核体内软语法.
主要成果:
- 精确地绘制了全基因组的低亲和度TF动图.
- 发现低亲和度的基因通过核体内相互作用进行合作,产生超大效应.
- 证明先合作性在不同TF度中增强了动机功能,增加了监管潜力.
结论:
- 低亲和度的TF动机可以准确地绘制,并具有重要的监管作用.
- 这些图案塑造了发育增强剂的特性,并且可能有助于进化过程中微调增强剂.
- 了解这些动机对于解释非编码变异至关重要.
相关概念视频
Master Transcription Regulators
7.6K
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...
7.6K
Spreading of Chromatin Modifications
9.3K
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...
9.3K
Chromatin Modification in iPS Cells
2.1K
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...
2.1K
Cooperative Binding of Transcription Regulators
7.1K
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...
7.1K
Heterochromatin
17.8K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
17.8K
Euchromatin
8.8K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
8.8K


