H2A.Z: view from the top.

For a couple of decades the chromatin field has endured undeserved neglect. Indeed, what could be so exciting about a monotonous repeating structure whose purpose in life was to package DNA? Chromatin glamour is triumphantly back, due to the realization that chromatin is a major player in the regulation of gene expression and other nuclear processes that occur on the DNA template. The dynamics of the structure that regulates transcription is itself regulated by a variety of complex processes, including histone postsynthetic modifications, chromatin remodeling, and the use of nonallelic histone variants. This review is an attempt to understand the mechanisms of action of the evolutionarily conserved variant H2A.Z, a player with a variety of seemingly unrelated, even contrary, functions. This attempt was prompted by the recent avalanche of genome-wide studies that provide insights that were unthinkable until very recently.