ZBTB24 is a conserved multifaceted transcription factor at genes and centromeres that governs the DNA methylation state and expression of satellite repeats
Since its discovery as a causative gene of the Immunodeficiency with Centromeric instability and Facial anomalies syndrome, ZBTB24 has emerged as a key player in DNA methylation, immunity and development. By extensively analyzing ZBTB24 genomic functions in ICF-relevant mouse and human cellular models, we document here its multiple facets as a transcription factor, with key roles in immune response-related genes expression and also in early embryonic development. Using a constitutive Zbtb24 ICF-like mutant and an auxin-inducible degron system in mouse embryonic stem cells, we showed that ZBTB24 is recruited to centromeric satellite DNA where it is required to establish and maintain the correct DNA methylation patterns through the recruitment of DNMT3B. The ability of ZBTB24 to occupy centromeric satellite DNA is conserved in human cells. Together, our results unveiled an essential and underappreciated role for ZBTB24 at mouse and human centromeric satellite repeat arrays by controlling their DNA methylation and transcription status.
Authors
- Michaël Weber (ORCID: https://orcid.org/0000-0003-3484-5821)
- Alice Jouneau (ORCID: https://orcid.org/0000-0001-5985-9862)
- Michaël Dumas (ORCID: https://orcid.org/0000-0001-8527-7006)
- S. John Mihic (ORCID: https://orcid.org/0000-0001-7631-5429)
- Thomas Dahlet
- Mathilde Bertrand (ORCID: https://orcid.org/0000-0001-7758-6159)
- Guillaume Velasco (ORCID: https://orcid.org/0000-0002-3620-8810)
- Giacomo Grillo (ORCID: https://orcid.org/0000-0003-4832-0954)
- Claire Francastel (ORCID: https://orcid.org/0000-0002-6353-4320)
- Ekaterina Boyarchuk (ORCID: https://orcid.org/0000-0002-7691-6547)
- Ivana Ivković (ORCID: https://orcid.org/0000-0002-1399-0977)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- École Nationale Vétérinaire d'Alfort (FR)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Sorbonne Université (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Epigénétique et Destin Cellulaire (FR)
- Biotechnologie et Signalisation Cellulaire (FR)
- Institut du Cerveau (FR)
- Biologie de la Reproduction, Environnement, Epigénétique et Développement (FR)
- Université de Strasbourg (FR)
- Epigenomics (Germany) (DE)
Publication Details
- Journal
- Human Molecular Genetics
- Published
- 2024-11-07
- DOI
- https://doi.org/10.1093/hmg/ddae163
- Citations
- 3
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 0.70