Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively...

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Detalhes bibliográficos
Autores: Urdinguio, Rocío G., Lopez, Virginia, Bayón, Gustavo F., Diaz de la Guardia, Rafael, Sierra, Marta I., García Toraño, Estela, Perez, Raúl F, García, María G., Carella, Antonella, Pruneda, Patricia C., Prieto, Cristina, Dmitrijeva, Marija, Santamarina, Pablo, Belmonte, Thalía, Mangas, Cristina, Diaconu, Elena, Ferrero, Cecilia, Tejedor, Juan Ramón, Fernandez Morera, Juan Luis, Bravo, Cristina, Bueno, Clara, Sanjuan Pla, Alejandra, Rodriguez, Ramón M., Suarez Alvarez, Beatriz, López Larrea, Carlos, Bernal, Teresa, Colado, Enrique, Balbín, Milagros, García Suarez, Olivia, Chiara, Maria Dolores, Sáenz de Santa María, Inés, Rodríguez, Francisco, Pando Sandoval, Ana, Rodrigo, Luis, Santos, Laura, Salas, Ana, Vallejo Díaz, Jesús, Carrera, Ana C., Rico, Daniel, Hernández López, Inmaculada, Vayá, Amparo, Ricart, José M., Seto, Edward, Sima Teruel, Núria, Vaquero, Alejandro, Valledor, Luis, Cañal, Maria Jesus, Pisano, David, Graña Castro, Osvaldo, Thomas, Tim, Voss, Anne K., Menéndez, Pablo, Villar Garea, Ana, Deutzmann, Rainer, Fernandez, Agustín F., Fraga, Mario F.
Formato: artículo
Fecha de publicación:2019
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/109874
Acesso em linha:https://hdl.handle.net/20.500.14352/109874
Access Level:acceso abierto
Palavra-chave:577.2
Biología molecular (Biología)
2415 Biología Molecular
Descrição
Resumo:Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death.

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