RT Journal Article
T1 Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma
A1 López, Virginia
A1 Tejedor, Juan Ramón
A1 Carella, Antonella
A1 García, María G.
A1 Santamarina-Ojeda, Pablo
A1 Pérez, Raúl F.
A1 Mangas, Cristina
A1 Urdinguio, Rocío G.
A1 Aranburu, Aitziber
A1 de la Nava, Daniel
A1 Corte-Torres, María D.
A1 Astudillo, Aurora
A1 Mollejo, Manuela
A1 Meléndez, Bárbara
A1 Fernández, Agustín F.
A1 Fraga, Mario F.
AB Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in adulthood. Epigenetic mechanisms are known to play a key role in GBM although the involvement of histone methyltransferase KMT5B and its mark H4K20me2 has remained largely unexplored. The present study shows that DNA hypermethylation and loss of DNA hydroxymethylation is associated with KMT5B downregulation and genome-wide reduction of H4K20me2 levels in a set of human GBM samples and cell lines as compared with non-tumoral specimens. Ectopic overexpression of KMT5B induced tumor suppressor-like features in vitro and in a mouse tumor xenograft model, as well as changes in the expression of several glioblastoma-related genes. H4K20me2 enrichment was found immediately upstream of the promoter regions of a subset of deregulated genes, thus suggesting a possible role for KMT5B in GBM through the epigenetic modulation of key target cancer genes.
PB Frontiers Media
YR 2021
FD 2021-08-10
LK https://hdl.handle.net/20.500.14352/109897
UL https://hdl.handle.net/20.500.14352/109897
LA eng
NO López, V., Tejedor, J. R., Carella, A., García, M. G., Santamarina-Ojeda, P., Pérez, R. F., Mangas, C., Urdinguio, R. G., Aranburu, A., de la Nava, D., Corte-Torres, M. D., Astudillo, A., Mollejo, M., Meléndez, B., Fernández, A. F., & Fraga, M. F. (2021). Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma. Frontiers in cell and developmental biology, 9, 671838. https://doi.org/10.3389/fcell.2021.671838
NO FUNDINGThis research was funded by the Health Institute Carlos III(Plan Nacional de I+D+I) cofounding FEDER (PI15/00892 andPI18/01527 to MF and AF); the Government of the Principalityof Asturias PCTI-Plan de Ciencia, Tecnología e Innovación deAsturias co-funding 2018–2022/FEDER (IDI/2018/146 to MF);AECC (PROYE18061FERN to MF); FGCSIC (0348_CIE_6_E toMF); Severo Ochoa Program BP17-165 to PS-O and BP17-114to RP); the Ministry of Economy and Competitiveness of Spain(VL, Juan de la Cierva fellowship IJCI-2015-23316; JT, Juan dela Cierva fellowship FJCI-2015-26965); FICYT (AC and MG);FINBA-ISPA (VL); and IUOPA (VL and CM). The IUOPA issupported by the Obra Social Cajastur-Liberbank, Spain.
NO Instituto de Salud Carlos III
NO Gobierno del Principado de Asturias
NO Ministerio de Economía y Competitividad de España
DS Docta Complutense
RD 5 abr 2025