RT Journal Article
SR Electronic
T1 A human-specific structural variation at the <em>ZNF558</em> locus controls a gene regulatory network during forebrain development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.18.255562
DO 10.1101/2020.08.18.255562
A1 Pia A. Johansson
A1 Per Ludvik Brattås
A1 Christopher H. Douse
A1 PingHsun Hsieh
A1 Julien Pontis
A1 Daniela Grassi
A1 Raquel Garza
A1 Marie E. Jönsson
A1 Diahann A. M. Atacho
A1 Karolina Pircs
A1 Feride Eren
A1 Yogita Sharma
A1 Jenny Johansson
A1 Didier Trono
A1 Evan E. Eichler
A1 Johan Jakobsson
YR 2020
UL http://biorxiv.org/content/early/2020/08/18/2020.08.18.255562.abstract
AB The human forebrain has expanded in size and complexity compared to that of chimpanzee despite limited changes in protein-coding genes, suggesting that gene 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 the mitophagy gene SPATA18, supporting a link between mitochondrial homeostasis and cortical expansion. The unusual on-off switch for ZNF558 expression resides in a downstream variable number tandem repeat (VNTR) that is contracted in humans relative to chimpanzee. Our data reveal the brain-specific co-option of a transposon-controlling KRAB-ZFP and how a human-specific regulatory network is established by a cis-acting structural genome variation. This represents a previously undescribed genetic mechanism in the evolution of the human brain.Competing Interest StatementThe authors have declared no competing interest.