Non-redundant functions of H2A.Z.1 and H2A.Z.2 in chromosome segregation and cell cycle progression

Abstract

SUMMARYH2A.Z is a H2A-type histone variant essential for many aspects of cell biology ranging from gene expression to genome stability. From deuterostomes, H2A.Z evolved into two paralogues H2A.Z.1 and H2A.Z.2 that differ by only three amino acids and are encoded by different genes (H2AFZ and H2AFV respectively). Despite the importance of this histone variant in development and cellular homeostasis, very little is known about the individual functions of each paralogue in mammals. Here we investigated the distinct roles of two paralogues in cell cycle regulation. Using a specific siRNA approach for each paralogue in human cells, we unveiled non-redundant functions for H2A.Z.1 and H2A.Z.2 in cell division: H2A.Z.1 regulates the expression of important cell cycle genes (including Myc and Ki-67) and its depletion leads to a G1 arrest, whereas H2A.Z.2 is essential for centromere integrity and function, thus playing a key role in chromosome segregation.