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| Home > Articles > Published articles > Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment |
| Home > Articles > Published articles > Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment |
(Instituto de Oncología de Asturias-IUOPA) (Centro de Investigación en Nanociencia y Nanotecnología (Oviedo, Astúries)) (Instituto de Oncología de Asturias-IUOPA) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Instituto de Oncología de Asturias-IUOPA) (Instituto de Oncología de Asturias-IUOPA) (Instituto de Oncología de Asturias-IUOPA) (Instituto de Oncología de Asturias-IUOPA) (Instituto de Oncología de Asturias-IUOPA) (Instituto de Oncología de Asturias-IUOPA) (Instituto de Oncología de Asturias-IUOPA) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Hospital Universitario Central de Asturias) (Hospital Universitario Central de Asturias) (Hospital Universitario Central de Asturias) (Hospital Universitario Central de Asturias) (Hospital Universitario Central de Asturias) (Hospital Universitario Central de Asturias) (Hospital Universitario Central de Asturias) (Universidad de Oviedo. Departamento de Bioquímica y Biología Molecular) (Hospital Universitario Central de Asturias) (Hospital Universitario Central de Asturias) (Instituto de Investigación Sanitaria del Principado de Asturias) (Newcastle University. Institute of Cellular Medicine) (Institut d'Investigació Biomèdica de Bellvitge) (Institut d'Investigació Biomèdica de Bellvitge) (Universidad de Oviedo. Facultad de Biología) (Universidad de Oviedo. Facultad de Biología) (Centro Nacional de Investigaciones Oncológicas) (University of Melbourne. Department of Medical Biology (Austràlia)) (University of Melbourne. Department of Medical Biology (Austràlia)) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (University of Regensburg) (Instituto de Oncología de Asturias-IUOPA) (Centro de Investigación en Nanociencia y Nanotecnología (Oviedo, Astúries))| Date: | 2019 |
| Abstract: | 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. |
| Grants: | Instituto de Salud Carlos III PI15-00892 Instituto de Salud Carlos III PI18-01527 Instituto de Salud Carlos III PI16-01318 Instituto de Salud Carlos III PI14-01244 Instituto de Salud Carlos III PI14-01191 Instituto de Salud Carlos III PI18-01527 European Commission 646903 Instituto de Salud Carlos III CP11-00131 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR330 Ministerio de Economía y Competitividad SAF-SAF2013-43065 Ministerio de Economía y Competitividad FJCI-2015-26965 Ministerio de Economía y Competitividad IJCI-2015-23316 |
| Note: | Altres ajuts: Fundación Científica de la AECC (to R.G.U.); Fundación Ramón Areces (to M.F.F); FICYT (to E.G.T., M.G.G., A.C.); Asturias Regional Government [GRUPIN14-052 to M.F.F.]; Gobierno del Principado de Asturias, PCTI-Plan de Ciencia, Tecnología e Innovación co-funding Fondos FEDER (grant number IDI/2018/146 to M.F.F. and IDI/2018/144 to C.L.); Asociación Española Contra el Cáncer [AECC-CI-2015]; P.M. acknowledges financial support from The Obra Social La Caixa-Fundaciò Josep Carreras. P.M. an investigator from the Spanish Cell Therapy cooperative network (TERCEL). The IUOPA is supported by the Obra Social Liberbank-Cajastur, Spain. |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Acetylation ; Animals ; Apoptosis ; Cell Differentiation ; Cells, Cultured ; Chromatin ; Epigenesis, Genetic ; Histones ; Humans ; Lysine ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Cells ; Protein Processing, Post-Translational ; Transcription, Genetic |
| Published in: | Nucleic acids research, Vol. 47 Núm. 10 (april 2019) , p. 5016-5037, ISSN 1362-4962 |
