Recent evidence by Bagert et al. have shown that cancer-associated histone mutations in the globular domain affect nucleosome stability (H2B-E71K/Q and H2B-E76K/Q) and nucleosome sliding (H2B-E113K/Q) and profoundly affects cell fate decision and differentiation of murine mesenchymal progenitor cells by altering gene expression of pathways involved in cell adhesion and pluripotency [16]. Here, H2BC21 is linked to cancer.