RT Journal Article
SR Electronic
T1 Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaba3200
DO 10.1126/sciadv.aba3200
VO 6
IS 35
A1 Turelli, Priscilla
A1 Playfoot, Christopher
A1 Grun, Dephine
A1 Raclot, Charlène
A1 Pontis, Julien
A1 Coudray, Alexandre
A1 Thorball, Christian
A1 Duc, Julien
A1 Pankevich, Eugenia V.
A1 Deplancke, Bart
A1 Busskamp, Volker
A1 Trono, Didier
YR 2020
UL http://advances.sciencemag.org/content/6/35/eaba3200.abstract
AB In the first days of embryogenesis, transposable element–embedded regulatory sequences (TEeRS) are silenced by Kruppel-associated box (KRAB) zinc finger proteins (KZFPs). Many TEeRS are subsequently co-opted in transcription networks, but how KZFPs influence this process is largely unknown. We identify ZNF417 and ZNF587 as primate-specific KZFPs repressing HERVK (human endogenous retrovirus K) and SVA (SINE-VNTR-Alu) integrants in human embryonic stem cells (ESCs). Expressed in specific regions of the human developing and adult brain, ZNF417/587 keep controlling TEeRS in ESC-derived neurons and brain organoids, secondarily influencing the differentiation and neurotransmission profile of neurons and preventing the induction of neurotoxic retroviral proteins and an interferon-like response. Thus, evolutionarily recent KZFPs and their TE targets partner up to influence human neuronal differentiation and physiology.