端粒位置效应 - - 跨越长距离,通过共同的 Alu 元素作为全基因组的表观遗传调节剂
Raphaël Chevalier1, Victor Murcia Pienkowski1, Nicolas Jullien2
1Aix Marseille Université, INSERM, MMG, Marseille Medical Genetics U1251, Marseille, France.
Aging cell
|March 11, 2025
概括
长距离的端粒位置效应 (TPE-OLD) 通过改变全基因组的循环来影响基因表达. 这项研究揭示了RBPJ和Alu元素调解TPE-OLD,影响细胞功能.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 染色体的保护帽子 - - 端粒通过表观遗传修饰影响基因组调节.
- 长距离端粒位置效应 (TPE-OLD) 描述了端粒长度和近距离如何通过长距离基因相互作用影响基因表达.
研究的目的:
- 阐明 TPE-OLD 背后的分子机制.
- 为了确定涉及TPE-OLD的cis-acting动机和trans-acting因素.
- 调查端粒缩短在通过TPE-OLD调节基因表达中的作用.
主要方法:
- 在纤维细胞和肌细胞/肌管中进行全基因组转录组和甲基组分析,其端粒长度不同.
- 整合omics数据以识别与TPE-OLD相关的基因组特征和监管因素.
- 与人类转录组数据集进行比较分析,包括基因型-组织表达 (GTEx) 项目.
主要成果:
- 识别一种常见的TPE-OLD依赖的cis-acting图案,作为绝缘体或增强剂.
- 发现了调节这些基因的跨合作伙伴,在端粒缩短时,在TPE-OLD位点显著地耗尽了RBPJ.
- 通过与现有的人类转录基因数据进行比较来验证发现.
结论:
- TPE-OLD在全基因组范围内运行,由RBPJ进行调解.
- RBPJ充当桥梁,将类似Alu的元素与端粒连接起来,以传递TPE-OLD.
- 可能涉及 Alu 元素和 RBPJ 的 TPE-OLD 可能在对生理和病理刺激的反应中协调全基因组端粒效应.
相关概念视频
Telomeres and Telomerase
23.2K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
23.2K
Position-effect Variegation
6.3K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
6.3K
Replication in Eukaryotes
170.5K
Overview
170.5K
Chromatin Position Affects Gene Expression
23.3K
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...
23.3K
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Non-LTR Retrotransposons
11.4K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.4K


