Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment
Por:
Urdinguio, RG, Lopez, V, Bayon, GF, de la Guardia, RD, Sierra, MI, Garcia-Torano, E, Perez, RF, Garcia, MG, Carella, A, Pruneda, PC, Prieto, C, Dmitrijeva, M, Santamarina, P, Belmonte, T, Mangas, C, Diaconu, E, Ferrero, C, Tejedor, JR, Fernandez-Morera, JL, Bravo, C, Bueno, C, Sanjuan-Pla, A, Rodriguez, RM, Suarez-Alvarez, B, Lopez-Larrea, C, Bernal, T, Colado, E, Balbin, M, Garcia-Suarez, O, Chiara, MD, Saenz-de-Santa-Maria, I, Rodriguez, F, Pando-Sandoval, A, Rodrigo, L, Santos, L, Salas, A, Vallejo-Diaz, J, Carrera, AC, Rico, D, Hernandez-Lopez, I, Vaya, A, Ricart, JM, Seto, E, Sima-Teruel, N, Vaquero, A, Valledor, L, Canal, MJ, Pisano, D, Grana-Castro, O, Thomas, T, Voss, AK, Menendez, P, Villar-Garea, A, Deutzmann, R, Fernandez, AF and Fraga, MF
Publicada:
4 jun 2019
Categoría:
Genetics
Resumen:
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.
Filiaciones:
Urdinguio, RG:
Univ Oviedo Principado Asturias, Nanomat & Nanotechnol Res Ctr CINN, CSIC, Oviedo, Asturias, Spain
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Lopez, V:
Univ Oviedo Principado Asturias, Nanomat & Nanotechnol Res Ctr CINN, CSIC, Oviedo, Asturias, Spain
Bayon, GF:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
de la Guardia, RD:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Barcelona, Spain
Univ Barcelona, Dept Biomed, Sch Med, Barcelona, Spain
Ctr Invest Biomed Red Canc CIBER ONC, Barcelona, Spain
Sierra, MI:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Garcia-Torano, E:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Perez, RF:
Univ Oviedo Principado Asturias, Nanomat & Nanotechnol Res Ctr CINN, CSIC, Oviedo, Asturias, Spain
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Garcia, MG:
Univ Oviedo Principado Asturias, Nanomat & Nanotechnol Res Ctr CINN, CSIC, Oviedo, Asturias, Spain
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Carella, A:
Univ Oviedo Principado Asturias, Nanomat & Nanotechnol Res Ctr CINN, CSIC, Oviedo, Asturias, Spain
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Pruneda, PC:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Prieto, C:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Dmitrijeva, M:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Santamarina, P:
Univ Oviedo Principado Asturias, Nanomat & Nanotechnol Res Ctr CINN, CSIC, Oviedo, Asturias, Spain
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Belmonte, T:
Univ Oviedo Principado Asturias, Nanomat & Nanotechnol Res Ctr CINN, CSIC, Oviedo, Asturias, Spain
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Mangas, C:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Diaconu, E:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Ferrero, C:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Tejedor, JR:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Fernandez-Morera, JL:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Bravo, C:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Barcelona, Spain
Univ Barcelona, Dept Biomed, Sch Med, Barcelona, Spain
Ctr Invest Biomed Red Canc CIBER ONC, Barcelona, Spain
Sanjuan-Pla, A:
Inst Invest Sanitaria La Fe IIS La Fe, Hematol Res Grp, Valencia 46026, Spain
Rodriguez, RM:
Hosp Univ Cent Asturias, Translat Immunol Lab, Inst Invest Sanitarias Principado Asturias ISPA, Dept Immunol, Oviedo, Spain
Suarez-Alvarez, B:
Hosp Univ Cent Asturias, Translat Immunol Lab, Inst Invest Sanitarias Principado Asturias ISPA, Dept Immunol, Oviedo, Spain
Lopez-Larrea, C:
Hosp Univ Cent Asturias, Translat Immunol Lab, Inst Invest Sanitarias Principado Asturias ISPA, Dept Immunol, Oviedo, Spain
Bernal, T:
Hosp Univ Cent Asturias, Serv Hematol, Oviedo, Spain
Colado, E:
Hosp Univ Cent Asturias, Serv Hematol, Oviedo, Spain
Balbin, M:
Univ Oviedo, Serv Mol Oncol, Hosp Univ Cent Asturias, Inst Univ Oncol Principado Asturias, Oviedo, Asturias, Spain
Garcia-Suarez, O:
Univ Oviedo, Dept Morphol & Cellular Biol, Fac Med, Oviedo, Asturias, Spain
Chiara, MD:
Univ Oviedo, Hosp Univ Cent Asturias, Inst Univ Oncol Principado Asturias, Otorhinolaryngol Serv,CIBERONC, Oviedo, Asturias, Spain
Saenz-de-Santa-Maria, I:
Univ Oviedo, Hosp Univ Cent Asturias, Inst Univ Oncol Principado Asturias, Otorhinolaryngol Serv,CIBERONC, Oviedo, Asturias, Spain
Rodriguez, F:
Univ Oviedo, Inst Univ Oncol IUOPA, Dept Bioquim & Biol Mol, Fac Med, Oviedo, Asturias, Spain
Pando-Sandoval, A:
Univ Oviedo, Hosp Univ Cent Asturias, Inst Nacl Silicosis, Area Pulmon,Fac Med, Ave Roma S-N, Oviedo 33011, Asturias, Spain
Rodrigo, L:
Univ Oviedo, Hosp Univ Cent Asturias, Gastroenterol Serv, Fac Med, Ave Roma S-N, Oviedo 33011, Asturias, Spain
Santos, L:
Fdn Invest Biosanitaria Asturias FINBA, Inst Invest Sanitaria Principado Asturias ISPA, Ave Roma S-N, Oviedo 33011, Asturias, Spain
Salas, A:
Univ Oviedo, Cytometry Serv, Serv Cient Tecn SCTs, Oviedo, Asturias, Spain
Vallejo-Diaz, J:
CSIC, Dept Immunol & Oncol, Natl Biotechnol Ctr, Madrid 28049, Spain
Carrera, AC:
CSIC, Dept Immunol & Oncol, Natl Biotechnol Ctr, Madrid 28049, Spain
Rico, D:
Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England
Hernandez-Lopez, I:
Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England
Vaya, A:
La Fe Univ Hosp, Hemorheol & Haemostasis Unit, Serv Clin Pathol, Valencia, Spain
Ricart, JM:
Quiron Clin, Dermatol Serv, Valencia, Spain
Seto, E:
George Washington Univ, Ctr Canc, Dept Biochem & Mol Med, Washington, DC 20037 USA
Sima-Teruel, N:
Bellvitge Biomed Res Inst IDIBELL, Chromatin Biol Lab, Canc Epigenet & Biol Program, Ave Gran Via Lhospitalet 199-203, Barcelona 08907, Spain
Vaquero, A:
Bellvitge Biomed Res Inst IDIBELL, Chromatin Biol Lab, Canc Epigenet & Biol Program, Ave Gran Via Lhospitalet 199-203, Barcelona 08907, Spain
Valledor, L:
Univ Oviedo, Dept Organisms & Syst Biol, Plant Physiol Lab, Fac Biol, Oviedo, Asturias, Spain
Canal, MJ:
Univ Oviedo, Dept Organisms & Syst Biol, Plant Physiol Lab, Fac Biol, Oviedo, Asturias, Spain
Pisano, D:
Spanish Natl Canc Res Ctr CNIO, Bioinformat Unit, Struct Biol & Biocomp Program, C Melchor Fernandez Almagro 3, Madrid 28029, Spain
Grana-Castro, O:
Spanish Natl Canc Res Ctr CNIO, Bioinformat Unit, Struct Biol & Biocomp Program, C Melchor Fernandez Almagro 3, Madrid 28029, Spain
Thomas, T:
Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia
Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia
Voss, AK:
Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia
Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia
:
Univ Barcelona, Josep Carreras Leukemia Res Inst, Sch Med, Barcelona, Spain
Univ Barcelona, Dept Biomed, Sch Med, Barcelona, Spain
Ctr Invest Biomed Red Canc CIBER ONC, Barcelona, Spain
Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain
Villar-Garea, A:
Univ Regensburg, Inst Biochem Genet & Microbiol, D-93053 Regensburg, Germany
Sanofi Aventis Deutschland GmbH, R&D, Ind Pk Hochst Bldg G878, D-65926 Frankfurt, Germany
Deutzmann, R:
Univ Regensburg, Inst Biochem Genet & Microbiol, D-93053 Regensburg, Germany
Fernandez, AF:
Univ Oviedo, Canc Epigenet Lab, Inst Oncol Asturias IUOPA, ISPA Hosp Univ Cent Asturias HUCA, Oviedo, Asturias, Spain
Fraga, MF:
Univ Oviedo Principado Asturias, Nanomat & Nanotechnol Res Ctr CINN, CSIC, Oviedo, Asturias, Spain
Green Published, gold
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