转录因子PAX5激活人类LINE1逆转录子,诱导细胞衰老
Huanyin Tang1, Jiaqing Yang1, Junhao Xu1
1Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
EMBO reports
|June 12, 2024
概括
转录因子PAX5在衰老细胞中激活长间隔元素1 (LINE1),促进衰老相关的分泌表型 (SASP). 长寿基因SIRT6抑制PAX5,为老化相关疾病提供了潜在的治疗点.
科学领域:
- 细胞衰老 细胞衰老
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 细胞衰老的特点是长间隔元素1 (LINE1) 的重新激活.
- 通过cGAS-STING通路,LINE1的重新激活会触发与衰老相关的分泌表型 (SASP).
- 调节LINE1在衰老中的重新激活的转录因子在很大程度上是未知的.
研究的目的:
- 确定与人类LINE1元素结合和调节的转录因子.
- 研究PAX5在LINE1激活和细胞衰老中的作用.
- 为了阐明SIRT6和PAX5在衰老中的调节关系.
主要方法:
- 在LINE1 5'-未翻译区域 (UTR) 中对保存的结合基因进行生物信息分析.
- 染色体免疫沉 (ChIP) 测定证实PAX5与LINE1 5'-UTR结合.
- 对PAX5和SIRT6操纵反应中的细胞衰老,SASP和基因表达的分析.
主要成果:
- PAX5被确定为一种转录因子,直接与LINE1 5'-UTR结合,在衰老细胞中结合增强.
- 在LINE1 5'-UTR的PAX5丰富促进细胞衰老和SASP通过激活LINE1转录.
- SIRT6直接与PAX5促进体结合,抑制其转录并抵消压力诱导的衰老;PAX5的过度表达可以克服SIRT6的抑制作用.
结论:
- 在细胞衰老中,PAX5是LINE1激活和SASP的关键驱动因素.
- 在SIRT6-PAX5轴中,SIRT6-PAX5轴在衰老过程中代表了一条新的调节途径.
- 向PAX5可能为老化相关疾病提供治疗策略.
相关概念视频
03:18Non-LTR Retrotransposons
11.5K
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...
11.5K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
02:57piRNA - Piwi-interacting RNAs
6.8K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
6.8K
03:08LTR Retrotransposons
17.5K
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
17.5K
01:29Somatic to iPS Cell Reprogramming
2.2K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.2K
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K