IMPPC Fundación Institut de Medicina Predictiva i Personalitzada del Càncer

The term ‘epigenetic' has been coined for information that does not rely on DNA sequence but can still be transmitted from mother to daughter cells. In cells DNA is packaged into chromatin. The structural unit of chromatin is DNA that is wrapped around a cylindric complex of 8 histone proteins. Modifications of these histones and of the DNA itself are now known to constitute a large part of the epigenetic memory of the cell. Another form of epigenetic modification is the complete exchange of a canonical histone for a variant protein. Among all known histone variants, macroH2A differs most from its canonical counterpart, but its function is poorly understood.
A project lead by CRG researchers Luciano Di Croce and Marcus Buschbeck (now IMPPC) could demonstrate a physiological function for macroH2A in the regulation of development and differentiation. As published in one of the Nature Journals, the investigators could show that macroH2A was not randomly distributed in the human genome but specifically sitting on genes that control developmental processes. In the presence of macroH2A these genes are rendered inactive until their appropriately timed activation triggers the release of macroH2A. The importance of this mechanism is exemplified by zebrafish that lack macroH2A. These fish display multiple defects including obvious body deformations.
Having identified the role of macroH2A in normal cells, a team at the IMPPC led by Marcus Buschbeck is now setting out to understand the regulation and function of macroH2A in cancer.