由PRC1和CTCF介导的过渡从平衡到活跃的染色体循环驱动双对应基因激活
Aflah Hanafiah1,2, Zhuangzhuang Geng1,2, Tingting Liu3,4
1Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA 17033.
bioRxiv : the preprint server for biology
|November 28, 2024
概括
多抑制复合体1 (PRC1) 和CCCTC-结合因子 (CTCF) 协同调节3D染色体结构. 这项研究揭示了PRC1.
科学领域:
- *表观遗传学和3D基因组组织.
- * 细胞分化和转录调节.
背景情况:
- *多抑制综合体1 (PRC1) 和CCCTC结合因子 (CTCF) 是3D染色体结构的关键调节者.
- *PRC1在染色质组织和基因激活中的作用,特别是在分化过程中,尚未完全理解.
- *空间色素结构包括分区,拓关联域 (TAD) 和动态色素循环.
研究的目的:
- * 为了研究含有Pcgf2的PRC1复合体 (cPRC1.2) 在细胞分化过程中激活双价基因的作用.
- *阐明PRC1,CTCF和3D染色体架构在控制细胞命运过渡中的相互作用.
- * 了解神经元分化过程中染色质循环是如何建立和重塑的.
主要方法:
- *Hi-C和虚拟4C分析以研究染色体循环形成和动态.
- * 在小鼠胚胎干细胞 (ESC) 中进行CRISPR/Cas9基因编辑,以评估Pcgf2.2的功能.
- *基因组分析以确定环和PcG体中的蛋白质丰富.
主要成果:
- * 规范性PRC1复合体1.2 (cPRC1.2) 在双价促销物中形成染色体循环,在准备激活时保持基因沉默.
- * 丢失Pcgf2会破坏ESC中的cPRC1.2循环,从而损害神经元分化所必需的基因的激活.
- *CTCF在cPRC1.2循环和PcG体处得到丰富,这表明在塑造染色质循环中具有合作作用.
- *神经元原生细胞 (NPC) 认同的确立包括从cPRC1.2介导的循环切换到CTCF介导的活性循环.
结论:
- *cPRC1.2通过形成平衡的染色体循环,在激活双价基因方面发挥了意想不到的作用.
- *PRC1和CTCF在细胞分化过程中合作建立和重塑3D染色质结构.
- * 通过PRC1和CTCF调解的染色质循环中的动态开关对于细胞命运过渡至关重要,例如神经元分化.
相关概念视频
Co-activators and Co-repressors
7.3K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
RNA Polymerase II Accessory Proteins
9.1K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K
Eukaryotic Transcription Activators
10.9K
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
10.9K
Chromatin Position Affects Gene Expression
23.2K
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...
23.2K
Combinatorial Gene Control
8.3K
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...
8.3K
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


