Primate-specific ZNF808 is Essential for Pancreatic Development in Humans

Overview

Journal Nat Genet

Specialty Genetics

Date 2023 Nov 17

PMID 37973953

Authors

Elisa De Franco

Nick D L Owens

Hossam Montaser

Matthew N Wakeling

Jonna Saarimaki-Vire

Athina Triantou

Hazem Ibrahim

Diego Balboa

Richard C Caswell

Rachel E Jennings

Jouni A Kvist

Matthew B Johnson

Sachin Muralidharan

Sian Ellard

Caroline F Wright

Sateesh Maddirevula

Fowzan S Alkuraya

Neil A Hanley

Sarah E Flanagan

Timo Otonkoski

Andrew T Hattersley

Michael Imbeault

Affiliations

Soon will be listed here.

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.

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