ZMYM2通过不同的共同调节复合体控制人类可转移元素的转录
Danielle J Owen1, Elisa Aguilar-Martinez1, Zongling Ji1
1Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester, United Kingdom.
eLife
|November 7, 2023
概括
指蛋白ZMYM2是一种转录抑制剂,与TRIM28等复合体相互作用,调节基因表达. 它主要通过控制拓关联域 (TADs) 内的逆转移子来影响编码基因.
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.
- 基因规则 基因规则
背景情况:
- ZMYM2 (指蛋白) 是一个转录调节器,对细胞身份至关重要.
- ZMYM2的失调与脏疾病和癌症有关.
- 众所周知,ZMYM2促进了转录抑制.
研究的目的:
- 为ZMYM2在转录抑制中的作用提供进一步的证据.
- 阐明ZMYM2在人类细胞中的功能和物理相互作用.
- 研究ZMYM2调节基因表达的机制.
主要方法:
- 染色体免疫沉测定用于识别ZMYM2相关复合体.
- 共同免疫沉以确认物理相互作用.
- 基因表达分析以评估调控效应.
- SUMOylation测试用于研究复杂的形成.
主要成果:
- ZMYM2形成了不同的染色质结合复合体,包括LSD1-CoREST-HDAC1核心压缩复合体.
- 发现了ZMYM2与ADNP以及ZMYM2与TRIM28/KAP1之间的新相互作用.
- ZMYM2-TRIM28复合体依赖于SUMOylation,与抑制色素相关.
- ZMYM2和TRIM28共同调节许多基因,主要是通过TAD内部的区域调节和逆转移子表达的直接控制.
- ZMYM2-ADNP复合体与SINEs相关,而ZMYM2-TRIM28复合体与LTR元素相关.
结论:
- ZMYM2作为转录抑制剂,部分通过其与核心抑制剂复合体的关联而起作用.
- ZMYM2-TRIM28相互作用在TADs内的区域基因调节中发挥着重要作用.
- ZMYM2直接调节逆转移子表达,这可能间接影响局部编码基因表达和染色质环境.
相关概念视频
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
Co-activators and Co-repressors
7.4K
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...
7.4K
RNA Polymerase II Accessory Proteins
9.2K
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...
9.2K
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
Cooperative Binding of Transcription Regulators
6.4K
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...
6.4K


