We show that H2A.Z is essential for the proliferation of human cancer and normal intestinal crypt cells and negatively controls the expression of a subset of differentiation markers, in cultured cells and mice.
The histone variant H2A.Z is involved in several processes such as transcriptional control, DNA repair, regulation of centromeric heterochromatin and, not surprisingly, is implicated in diseases such as cancer.
The human genome encodes four YEATS domain proteins, including GAS41, a component of chromatin remodelers responsible for H2A.Z deposition onto chromatin; however, the importance of the GAS41 YEATS domain in human cancer remains largely unknown.
The present review focuses on the H2A variants H2A.Z, H2A.X, and macroH2A, and summarizes their functions in chromatin and how these are linked to cancer development and progression.
Gene deregulation in cancer is also associated with a reorganization of acH2A.Z and H2A.Z nucleosome occupancy across the promoter region and TSS of genes.
Studying tumor suppressor genes (TSGs) silenced in cancer cell lines, we find that when active, these promoters are associated with H2A.Z but become enriched for macroH2A1 once silenced.
A recent study provides a new insight into the role of H2A.Z within the context of cancer-related genes and further corroborates the emerging link between dysfunction of this histone variant and cancer.