Suchergebnisse

This work has been financially supported by the Plan Nacional de I + D + I 2008–2011/2013–2016/FEDER (PI11/01728 to A.F.F.; PI12/01080 and PI15/00892 to M.F.F.; PI 12/0615 to J.A.R.; PI05/2217 and PI08/0029 to J.G-C); the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (Miguel Servet contract: CP11/00131 to A.F.F.); IUOPA (to G.F.B. and M.S); Fundacion Cientifica de la AECC (to R.G.U.); Fundación Ramón Areces (to M.F.F); and FICYT (to E.G.T., M.G.G and A.C.);the Madrid Regional Government (S-BIO-02042006 and S2010/BMD-2420 to J.G-C) and the Asturias Regional Government (GRUPIN14-052 to M.F.F.). The IUOPA is supported by the Obra Social Cajastur, Spain. ; Toraño, E.G., Bayón, G.F., del Real, Á., Sierra, M.I., García, M.G., Carella, A., Belmonte, T., Urdinguio, R.G., Cubillo, I., García-Castro, J., Delgado-Calle, J., Pérez-Campo, F.M., Riancho, J.A., Fraga, M.F., Fernández, A.F.

This work has been financially supported by: the Plan Nacional de I+D+I 2013-2016/FEDER (PI15/00892 to M.F.F. and A.F.F.); the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, and the Plan Nacional de I+D+I 2008-2011/FEDER (CP11/00131 to A.F.F.); IUOPA (to G.F.B., M.I.S. and C.M.); the Fundación Científica de la AECC (to R.G.U.); FICYT (to M.G.G. and A.C.); and the Asturias Regional Government (GRUPIN14-052 to M.F.F.). A.F.F. is also supported from Ministerio de Economía y Competitividad and the European Regional Development Fund (FEDER), Programa Retos de la Sociedad 2015 (RTC-2015-3393-1). The IUOPA is supported by the Obra Social CajasturLiberbank, Spain. ; García, M.G., Carella, A., Urdinguio, R.G., Bayón, G.F., Lopez, V., Tejedor, J.R., Sierra, M.I., García-Toraño, E., Santamarina, P., Perez, R.F., Mangas, C., Astudillo, A., Corte-Torres, M.D., Sáenz-de-Santa-María, I., Chiara, M.-D., Fernández, A.F., Fraga, M.F.

Plan Nacional de I+D+I co-funding FEDER [PI15/00892 and PI18/01527 to M.F.F. and A.F.F.; PI16/01318 and PI14/01244 to C.L.]; ISCIII-Subdireccion General de Evaluación y Fomento de la Investigación, and Plan ´ Nacional de I+D+I 2008–2011/FEDER [CP11/00131 to A.F.F.]; IUOPA (to G.F.B. and M.I.S.); Fundación Científica de la AECC (to R.G.U.); Ministry of Economy and Competitiveness Juan de la Cierva postdoctoral fellowships [FJCI-2015-26965 to J.R.T., IJCI-2015- 23316 to V.L.]; 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.); Spanish Ministry of Economy and Competitiveness [SAF-SAF2013-43065 to P.M.]; Asociación Española Contra el Cáncer [AECC-CI-2015]; FERO Foundation, and the ISCIII [PI14-01191 to C.B.]; P.M. acknowledges financial support from The Obra Social La Caixa Fundación Josep Carreras and The Generalitat de Catalunya (SGR330). P.M. an investigator from the Spanish Cell Therapy cooperative network (TERCEL). The IUOPA is supported by the Obra Social Liberbank-Cajastur, Spain. Funding for open access charge: Plan Nacional de I+D+I co-funding FEDER [PI18/01527]. ; Urdinguio, R.G., Lopez, V., Bayón, G.F., Diaz De La Guardia, R., Sierra, M.I., García-Toraño, E., Perez, R.F., García, M.G., Carella, A., Pruneda, P.C., Prieto, C., Dmitrijeva, M., Santamarina, P., Belmonte, T., Mangas, C., Diaconu, E., Ferrero, C., Tejedor, J.R., Fernandez-Morera, J.L., Bravo, C., Bueno, C., Sanjuan-Pla, A., Rodriguez, R.M., Suarez-Alvarez, B., López-Larrea, C., Bernal, T., Colado, E., Balbín, M., García-Suarez, O., Chiara, M.D., Sáenz-De-Santa-María, I., Rodríguez, F., Pando-Sandoval, A., Rodrigo, L., Santos, L., Salas, A., Vallejo-Díaz, J., C Carrera, A., Rico, D., Hernández-López, I., Vayá, A., Ricart, J.M., Seto, E., Sima-Teruel, N., Vaquero, A., Valledor, L., Cañal, M.J., Pisano, D., ...

Ten-eleven translocation (TET) enzymes are frequently deregulated in cancer, but the underlying molecular mechanisms are still poorly understood. Here we report that TET2 shows frequent epigenetic alterations in human glioblastoma including DNA hypermethylation and hypo-hydroxymethylation, as well as loss of histone acetylation. Ectopic overexpression of TET2 regulated neural differentiation in glioblastoma cell lines and impaired tumor growth. Our results suggest that epigenetic dysregulation of TET2 plays a role in human glioblastoma. ; This work has been financially supported by: the Plan Nacional de I+D+I 2013-2016/FEDER (PI15/00892 to M.F.F. and A.F.F.); the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, and the Plan Nacional de I+D+I 2008-2011/FEDER (CP11/00131 to A.F.F.); IUOPA (to G.F.B., M.I.S. and C.M.); the Fundación Científica de la AECC (to R.G.U.); FICYT (to M.G.G. and A.C.); and the Asturias Regional Government (GRUPIN14-052 to M.F.F.). A.F.F. is also supported from Ministerio de Economía y Competitividad and the European Regional Development Fund (FEDER), Programa Retos de la Sociedad 2015 (RTC-2015-3393-1). The IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain. ; Peer Reviewed

This work has been financially supported by the Plan Nacional de I+D+I 2013-2016/FEDER (PI15/00892 to M.F.F. and A.F.F.), the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (Miguel Servet contract CP11/00131 to A.F.F.); the Asturias Regional Government (GRUPIN14-052 to M.F.F.); FICYT (A.C. and M.G.); the Ministry of Economy and Competitiveness of Spain (J.R.T., Juan de la Cierva fellowship FJCI-2015-26965, V.L., Juan de la Cierva fellowship IJCI-2015-23316); Fundación Científica de la AECC (to R.G.U.); FINBA-ISPA (R.F.P.); IUOPA (G.F.B. and C.M.) and Fundación Ramón Areces (M.F.F.). A.F.F. is also financially supported by the Ministry of Economy and Competitiveness of Spain, the European Regional Development Fund (FEDER) and the Programa Retos de la Sociedad (RTC-2015-3393-1). The IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain.

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. ; Plan Nacional de I+D+I co-funding FEDER [PI15/00892 and PI18/01527 to M.F.F. and A.F.F.; PI16/01318 and PI14/01244 to C.L.]; ISCIII-Subdireccion General de Evaluacion y Fomento de la Investigacion, and Plan Nacional de I+D+I 2008–2011/FEDER [CP11/00131 to A.F.F.]; IUOPA (to G.F.B. and M.I.S.); Fundacion Cientifica de la AECC (to R.G.U.); Ministry of Economy and Competitiveness Juan de la Cierva postdoctoral fellowships [FJCI-2015-26965 to J.R.T., IJCI-2015- 23316 to V.L.]; Fundacion Ramon 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, Tecnologia e Innovacion co-funding Fondos FEDER (grant number IDI/2018/146 to M.F.F. and IDI/2018/144 to C.L.); Deutsche Forschungsgemeinschaft (DFG) [SFB960 to A.V.G., R.D.]; European Research Council [CoG-2014-646903]; Spanish Ministry of Economy and Competitiveness [SAF-SAF2013-43065 to P.M.]; Asociacion Española Contra el Cancer [AECC-CI-2015]; FERO Foundation, and the ISCIII [PI14-01191 to C.B.]; P.M. acknowledges financial support from The Obra Social La Caixa Fundacio Josep Carreras and The Generalitat de Catalunya (SGR330). P.M. an investigator from the Spanish Cell Therapy cooperative network (TERCEL). The IUOPA is supported by the Obra Social Liberbank-Cajastur, Spain. Funding for open access charge: Plan Nacional de I+D+I co-funding FEDER [PI18/01527].