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GABRIELLA SCHIERA

Oligodendroglioma cells synthesize the differentiation-specific linker histone H1Ëš and release it into the extracellular environment through shed vesicles

  • Authors: Schiera, G; Di Liegro, CM; Saladino, P; Pitti, R; Savettieri, G; Proia, P; Di Liegro, I.
  • Publication year: 2013
  • Type: Articolo in rivista (Articolo in rivista)
  • OA Link: http://hdl.handle.net/10447/88503

Abstract

Chromatin remodelling can be involved in some of the epigenetic modifications found in tumor cells. One of the mechanisms at the basis of chromatin dynamics is likely to be synthesis and incorporation of replacement histone variants, such as the H1Ëš linker histone. Regulation of the expression of this protein can thus be critical in tumorigenesis. In developing brain, H1Ëš expression is mainly regulated at the post-transcriptional level and RNA-binding proteins (RBPs) are involved. In the past, attention mainly focused on the whole brain or isolated neurons and little information is available on H1Ëš expression in other brain cells. Even less is known relating to tumor glial cells. In this study we report that, like in maturing brain and isolated neurons, H1Ëš synthesis sharply increases in differentiating astrocytes growing in a serum-free medium, while the corresponding mRNA decreases. Unexpectedly, in tumor glial cells both H1Ëš RNA and protein are highly expressed, in spite of the fact that H1Ëš is considered a differentiation-specific histone variant. Persistence of H1Ëš mRNA in oligodendroglioma cells is accompanied by high levels of H1Ëš RNA-binding activities which seem to be present, at least in part, also in actively proliferating, but not in differentiating, astrocytes. Finally, we report that oligodendroglioma cells, but not astrocytes, release H1Ëš protein into the culture medium by shedding extracellular vesicles. These findings suggest that deregulation of H1Ëš histone expression can be linked to tumorigenesis.