SMARCAD1 and TOPBP1 contribute to heterochromatin maintenance at the transition from the 2C-like to the pluripotent state

Chromocenters are established after the 2-cell (2C) stage during mouse embryonic development, but the factors that mediate chromocenter formation remain largely unknown. To identify regulators of 2C heterochromatin establishment, we generated an inducible system to convert embryonic stem cells (ESCs...

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Detalles Bibliográficos
Autores: Sebastián Pérez, Rubén, Nakagawa, Shoma, Tu, Xiaochuan, Aranda Aragón, Sergio, Pesaresi, Martina, 1991-, Gómez García, Pablo, Alcoverro-Bertran, Marc, Gómez Vázquez, José Luis, Carnevali, Davide, Borràs, Eva, Sabidó Aguadé, Eduard, 1981-, Martin, Laura, Nissim Rafinia, Malka, Meshorer, Eran, Neguembor, Maria Victoria, Di Croce, Luciano, Cosma, Maria Pia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/58213
Acceso en línea:http://hdl.handle.net/10230/58213
http://dx.doi.org/10.7554/eLife.87742.3
Access Level:acceso abierto
Palabra clave:Cromosomes
Cromatina
Genètica
Descripción
Sumario:Chromocenters are established after the 2-cell (2C) stage during mouse embryonic development, but the factors that mediate chromocenter formation remain largely unknown. To identify regulators of 2C heterochromatin establishment, we generated an inducible system to convert embryonic stem cells (ESCs) to 2C-like cells. This conversion is marked by a global reorganization and dispersion of H3K9me3-heterochromatin foci, which are then reversibly formed upon re-entry into pluripotency. Profiling the chromatin-bound proteome (chromatome) by genome capture of ESCs transitioning to 2C-like cells, we uncover chromatin regulators involved in de novo heterochromatin formation. We identified TOPBP1 and investigated its binding partner SMARCAD1. SMARCAD1 and TOPBP1 associate with H3K9me3-heterochromatin in ESCs. Interestingly, the nuclear localization of SMARCAD1 is lost in 2C-like cells. SMARCAD1 or TOPBP1 depletion in mouse embryos lead to developmental arrest, reduction of H3K9me3 and remodeling of heterochromatin foci. Collectively, our findings contribute to comprehending the maintenance of chromocenters during early development.

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