A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819

Fernandes, L. P. et al. (2022) A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819. Science Advances, 8(43), eabp8085. (doi: 10.1126/sciadv.abp8085) (PMID:36306355) (PMCID:PMC9616502)

Abstract

Mammalian genomes are a battleground for genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs). We asked whether KZFPs can regulate cell fate by using ZFP819, which targets a satellite DNA array, ZP3AR. ZP3AR coats megabase regions of chromosome 7 encompassing genes encoding ZSCAN4, a master transcription factor of totipotency. Depleting ZFP819 in mouse embryonic stem cells (mESCs) causes them to transition to a 2-cell (2C)–like state, whereby the ZP3AR array switches from a poised to an active enhancer state. This is accompanied by a global erosion of heterochromatin roadblocks, which we link to decreased SETDB1 stability. These events result in transcription of active LINE-1 elements and impaired differentiation. In summary, ZFP819 and TRIM28 partner up to close chromatin across Zscan4 , to promote exit from totipotency. We propose that satellite DNAs may control developmental fate transitions by barcoding and switching off master transcription factor genes.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gifford, Dr Robert
• Authors: Fernandes, L. P., Enriquez-Gasca, R., Gould, P. A., Holt, J. H., Conde, L., Ecco, G., Herrero, J., Gifford, R., Trono, D., Kassiotis, G., and Rowe, H. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Science Advances
• Publisher: American Association for the Advancement of Science
• ISSN: 2375-2548
• ISSN (Online): 2375-2548
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Science Advances 8(43): eabp8085
• Publisher Policy: Reproduced under a Creative Commons License