Primate-specific ZNF808 is essential for pancreatic development in humans.
Nat Genet
; 55(12): 2075-2081, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37973953
ABSTRACT
Identifying genes linked to extreme phenotypes in humans has the potential to highlight biological processes not shared with all other mammals. Here, we report the identification of homozygous loss-of-function variants in the primate-specific gene ZNF808 as a cause of pancreatic agenesis. ZNF808 is a member of the KRAB zinc finger protein family, a large and rapidly evolving group of epigenetic silencers which target transposable elements. We show that loss of ZNF808 in vitro results in aberrant activation of regulatory potential contained in the primate-specific transposable elements it represses during early pancreas development. This leads to inappropriate specification of cell fate with induction of genes associated with liver identity. Our results highlight the essential role of ZNF808 in pancreatic development in humans and the contribution of primate-specific regions of the human genome to congenital developmental disease.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pâncreas
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Anormalidades Congênitas
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Elementos de DNA Transponíveis
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Proteínas de Ligação a DNA
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article