通过NSL复合体进行的转录调节,可以使纤毛细胞和非纤毛细胞中的IFT功能多样化
Tsz Hong Tsang1,2,3, Meike Wiese1, Martin Helmstädter4
1Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Science advances
|August 25, 2023
概括
NSL复合体对于分化细胞至关重要,调节功能和细胞运输. 它的干扰会导致严重的损伤和细胞功能障碍,突出显示其在早期发育之外的多样性作用.
科学领域:
- 细胞生物学 细胞生物学
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 基因组核矩阵相关转录调节 (NSL) 复合体对于早期发育至关重要,但其在分化细胞中的功能尚不清楚.
- 了解NSL复合体在专门的细胞中所扮演的角色,对于理解组织稳态和疾病至关重要.
研究的目的:
- 研究NSL复合体在分化细胞中的功能,特别是在脏细胞和纤维细胞中.
- 阐明NSL复合体成员KANSL2和KANSL3影响功能和细胞过程的机制.
- 确定KANSL2中的特定域在NSL复杂组合和功能中的作用.
主要方法:
- 采用脏特异型模型,在转移后的 podocytes 中删除 NSL 复合体成员 (KANSL2,KANSL3).
- 在两个差异化的细胞类型 (脏细胞和状纤维细胞) 之间进行了系统比较.
- 分析了内运输基因,毛形成,声波刺通路活动,微管动力学和基因表达.
- 通过过度表达研究,研究了KANSL2双指 (ZF-ZF) 域的功能意义.
主要成果:
- 细胞中KANSL2或KANSL3的删除导致严重的功能障碍.
- NSL复合体在分裂和不分裂的分化细胞中调节内运输基因.
- 纤维细胞中NSL复合体的切除导致毛损失和声波刺信号受损.
- 在非化细胞中,NSL复合体损失导致微管体动态变化和功能消失.
- 过度表达野生型KANSL2,但不是ZF-ZF突变,拯救了转录缺陷,表明该域对复杂组装和功能的重要性.
结论:
- 该NSL复合体在维持分化细胞的功能方面发挥着至关重要的,以前未知的作用.
- NSL复合体表现出功能分支,使其作用适应不同细胞类型 (化与非化) 的特定需求.
- KANSL2的双指 (ZF-ZF) 域对于NSL复合组合及其在分化细胞中的调节功能至关重要.
相关概念视频
Regulation of Expression at Multiple Steps
943
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
943
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Cis-regulatory Sequences
9.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
9.9K
Regulation of Expression Occurs at Multiple Steps
22.8K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.8K
Transcription
147.2K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
147.2K
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


