期刊
CELL STEM CELL
卷 29, 期 1, 页码 52-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2021.09.008
关键词
-
资金
- Swedish Research Council [2018-02694]
- Swedish Brain Foundation [FO2019-0098]
- Cancerfonden [190326]
- Barncancerfonden [PR2017-0053]
- Swedish Society for Medical Research [S19-0100]
- Swedish Government Initiative for Strategic Research Areas (MultiPark StemTherapy)
- Swedish Research Council [2018-02694] Funding Source: Swedish Research Council
Despite limited changes in protein-coding genes, the human forebrain has expanded in size and complexity compared to chimpanzees. This suggests that gene expression regulation, rather than genetic changes, plays a significant role in brain evolution. Researchers have identified a transcription factor called ZNF558 that is expressed in human forebrain neural progenitor cells but not in chimpanzees. ZNF558 functions in mitochondrial homeostasis and influences developmental timing during early human brain development. Its expression is controlled by a variable number tandem repeat, which is longer in chimpanzees and shows variability within the human population. This study provides mechanistic insights into how regulatory networks are established through structural variations, affecting human brain evolution.
The human forebrain has expanded in size and complexity compared to chimpanzees despite limited changes in protein-coding genes, suggesting that gene expression regulation is an important driver of brain evolution. Here, we identify a KRAB-ZFP transcription factor, ZNF558, that is expressed in human but not chimpanzee forebrain neural progenitor cells. ZNF558 evolved as a suppressor of LINE-1 transposons but has been co-opted to regulate a single target, the mitophagy gene SPATA18. ZNF558 plays a role in mitochondrial homeostasis, and loss-of-function experiments in cerebral organoids suggests that ZNF558 influences developmental timing during early human brain development. Expression of ZNF558 is controlled by the size of a variable number tandem repeat that is longer in chimpanzees compared to humans, and variable in the human population. Thus, this work provides mechanistic insight into how a cis-acting structural variation establishes a regulatory network that affects human brain evolution.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据