The PRC2-associated factor EPOP is required for Hox gene regulation during axial development in mice

The Polycomb repressive complex 2 (PRC2) is an essential modulator of gene repression. We previously reported that, in mouse embryonic stem cells, PRC2 associates with elonginB/C through EPOP, which allows for low-level expression of target genes. Here we investigate the role of EPOP in vivo by gene...

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Detalles Bibliográficos
Autores: Mocavini, Ivano|||0000-0003-1164-9908, Mallol, Anna|||0000-0001-7366-0980, Gutierrez, Arantxa, Chammas, Paul, Carretero i Romay, Ana|||0000-0001-9377-4926, Dias, André, Blanco, Enrique|||0000-0001-6261-7370, Rodriguez Arce, Irene, Mallo, Moises, Di Croce, Luciano|||0000-0003-3488-6228, Payer, Bernhard|||0000-0002-4694-2082
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:321604
Acceso en línea:https://ddd.uab.cat/record/321604
https://dx.doi.org/urn:doi:10.1016/j.ydbio.2025.08.014
Access Level:acceso abierto
Palabra clave:Body patterning
EPOP
Hox genes
Polycomb
PRC2
Descripción
Sumario:The Polycomb repressive complex 2 (PRC2) is an essential modulator of gene repression. We previously reported that, in mouse embryonic stem cells, PRC2 associates with elonginB/C through EPOP, which allows for low-level expression of target genes. Here we investigate the role of EPOP in vivo by generating a mouse knockout (KO) model. We show that Epop KO mice are viable and fertile but display highly penetrant posterior homeotic transformations of the axial skeleton, which can be partially recapitulated by deletion of only the maternal allele. Epop-depleted embryos present a shift of the anterior boundary of expression of certain Hox genes. Tissue-specific RNA sequencing of embryos suggests that the Hox activation defect originates at the level of the presomitic mesoderm. Overall, we find that EPOP prevents premature activation of a subset of Hox genes, and that this is required for correct body patterning along the antero-posterior axis.