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

2019; Oxford University Press; Volume: 47; Issue: 10 Linguagem: Inglês

10.1093/nar/gkz195

1362-4962

Rocío G. Urdinguio, Virginia López, Gustavo F. Bayón, Rafael Díaz de la Guardia, Marta Sierra, Estela García‐Toraño, Raúl F. Pérez, María González García, Antonella Carella, Patricia C Pruneda, Cristina Prieto, Marija Dmitrijeva, Pablo Santamarina‐Ojeda, Thalía Belmonte, Cristina Mangas, Elena Lavinia Diaconu, Cecilia Ferrero, Juan Ramón Tejedor, Juan Luís Fernández-Morera, Cristina Bravo, Clara Bueno, Alejandra Sanjuán-Pla, Ramón María Alvargonzález Rodríguez, Beatriz Suárez-Álvarez, Carlos López‐Larrea, Teresa Bernal, Enrique Colado, Milagros Balbı́n, Olivia García‐Suárez, María‐Dolores Chiara, Inés Sáenz‐de‐Santa‐María, Francisco Rodríguez, Ana Pando‐Sandoval, Luı́s Rodrigo, Laura Santos, Ana Salas, Jesús Vallejo-Díaz, Ana C. Carrera, Daniel Rico, Inmaculada Hernández-López, Amparo Vayá, José M. Ricart, Edward Seto, Núria Sima, Alejandro Vaquero, Luís Valledor, María Jesús Cañal, David G. Pisano, Osvaldo Graña‐Castro, Tim Thomas, Anne K. Voss, Pablo Menéndez, Ana Villar‐Garea, Rainer Deutzmann, Agustín F. Fernández, Mario F. Fraga,

Genomics and Chromatin Dynamics

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.