生物
前脑
转录因子
基因
遗传学
基因座(遗传学)
人脑
基因调控网络
表观遗传学
基因表达调控
神经科学
基因表达
中枢神经系统
作者
Peter Johansson,Per Ludvik Brattås,Christopher H. Douse,PingHsun Hsieh,Anita Adami,Julien Pontis,Daniela Grassi,Raquel Garza,Edoardo Sozzi,Luis Rodrigo Cataldo,Marie E. Jönsson,Diahann A. M. Atacho,Karolina Pircs,Feride Eren,Yogita Sharma,Jenny Johansson,Alessandro Fiorenzano,Malin Parmar,Malin Fex,Didier Trono,Evan E. Eichler,Johan Jakobsson
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2022-01-01
卷期号:29 (1): 52-69.e8
被引量:40
标识
DOI:10.1016/j.stem.2021.09.008
摘要
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.
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