AUTHOR=López Virginia , Tejedor Juan Ramón , Carella Antonella , García María G. , Santamarina-Ojeda Pablo , Pérez Raúl F. , Mangas Cristina , Urdinguio Rocío G. , Aranburu Aitziber , de la Nava Daniel , Corte-Torres María D. , Astudillo Aurora , Mollejo Manuela , Meléndez Bárbara , Fernández Agustín F. , Fraga Mario F. 

TITLE=Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.671838

DOI=10.3389/fcell.2021.671838

ISSN=2296-634X

ABSTRACT=<p>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 <italic>KMT5B</italic> and its mark H4K20me2 has remained largely unexplored. The present study shows that DNA hypermethylation and loss of DNA hydroxymethylation is associated with <italic>KMT5B</italic> 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 <italic>KMT5B</italic> induced tumor suppressor-like features <italic>in vitro</italic> 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 <italic>KMT5B</italic> in GBM through the epigenetic modulation of key target cancer genes.</p>