Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons

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 ident...

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Detalles Bibliográficos
Autores principales: Turelli, Priscilla, Playfoot, Christopher, Grun, Dephine, Raclot, Charlène, Pontis, Julien, Coudray, Alexandre, Thorball, Christian, Duc, Julien, Pankevich, Eugenia V., Deplancke, Bart, Busskamp, Volker, Trono, Didier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455193/
https://www.ncbi.nlm.nih.gov/pubmed/32923624
http://dx.doi.org/10.1126/sciadv.aba3200
Descripción
Sumario: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.

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