Transcriptomics

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Structural variation at the ZNF558 locus controls a gene regulatory network in human brain development


ABSTRACT: The human forebrain has expanded in size and complexitycompared to that of chimpanzeedespite limited changesinprotein-coding genes, suggesting that gene regulation is an importantdriver of brain evolution. Here we identify a KRAB-ZFPtranscription factor, ZNF558, that isexpressed in human but not chimpanzee forebrain neural progenitor cells. ZNF558 evolved asa suppressor of LINE-1 transposons but has been co-opted to regulate the mitophagy geneSPATA18, supporting a link between mitochondrial homeostasis andcorticalexpansion. Theunusual on-off switchforZNF558expression resides in a downstream variable number tandemrepeat (VNTR) that is contracted in humans relative to chimpanzee.Our data reveal the brain-specific co-option of a transposon-controllingKRAB-ZFPand how a human-specificregulatory network is established by acis-acting structural genome variation. Thisrepresentsapreviouslyundescribedgenetic mechanisminthe evolution of the human brain.

ORGANISM(S): Homo sapiens Pan troglodytes

PROVIDER: GSE182224 | GEO | 2021/09/19

REPOSITORIES: GEO

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