2017 May 1

JCS cover for a new function of tumor suppressive histone variant identified

The histone variants macroH2A are tumor suppressors that are down regulated or lost in several solid cancers and leukemia

The histone variants macroH2A are tumor suppressors that are downregulated or lost in several solid cancers and leukemia. Dr. Julien Douet from the team headed by Marcus Buschbeck has now identified a major function for these proteins that has great potential to provide an explanation for its role in cancer. 

The genomic DNA of a cell is stored in its nucleus as large DNA-protein complex called chromatin. The nucleosome is the building block of chromatin and consists of DNA wrapped around a protein core. Although only 1% of all nucleosomes contain macroH2A, it is essential for the correct organization of the nucleus. The loss of macroH2A induces large-scale reorganizations of the nucleus. In particular, the dense packaging of inactive regions referred to heterochromatin and visible as dark matter in the electron microscopy is entire lost. In their paper that was just published in the Journal of Cell Science, the authors further dissect the molecular mechanism underlying this drastic phenotype. Similar losses of dense heterochromatin are characteristic for leukemia cells and also occur during somatic cell reprogramming, a process inhibited by macroH2A. Taken together this study demonstrated an entirely novel aspect for the function of a histone variant, providing a framework for the understanding of its roles in cellular reprogramming, development and cancer.

Link to publication research: here

Legend: Electron microscopy images of control and macroH2A depleted cells demonstrate a major role in nuclear organization.