Histone H2A.Z has a conserved function that is distinct from that of the major H2A sequence variants

Abstract

Saccharomyces cerevisiae contains three genes that encode members of the histone H2A gene family. The last of these to be discovered, HTZ1 (also known as HTA3), encodes a member of the highly conserved H2A.Z class of histones. Little is known about how its in vivo function compares with that of the better studied genes (HTA1 and HTA2) encoding the two major H2As. We show here that, while the HTZ1 gene encoding H2A.Z is not essential in budding yeast, its disruption results in slow growth and formamide sensitivity. Using plasmid shuffle experiments, we show that the major H2A genes cannot provide the function of HTZ1 and the HTZ1 gene cannot provide the essential function of the genes encoding the major H2As. We also demonstrate for the first time that H2A.Z genes are functionally conserved by showing that the gene encoding the H2A.Z variant of the ciliated protozoan TETRAHYMENA: thermophila is able to rescue the phenotypes associated with disruption of the yeast HTZ1 gene. Thus, the functions of H2A.Z are distinct from those of the major H2As and are highly conserved.

Reconciling the positive and negative roles of histone H2A.Z in gene transcription

“…In budding yeast, loss of H2A.Z leads to defects in transcriptional activation, alterations in transcriptional silencing, and increased chromosome loss. [21][22][23][24][25][26] In mammalian cells, H2A.Z is important for chromosome segregation, centromeric functions and transcriptional regulation. [27][28][29][30] To date, H2A.Z has been reported to be acetylated, ubiquitylated and sumoylated, but little is known about the functional role of these post-translational modifications.…”

Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell cycle checkpoint adaptationin response to DNA damage

“…Since ATP-dependent chromatin remodeling enzymes can catalyze the replacement of histone H2A variants (Mizuguchi et al 2003;Kusch et al 2004), we considered an alternative model in which loss of H2AX-phos in the ino80⌬ mutant might be the result of a histone replacement event, involving either unphosphorylated H2AX or the Htz1p histone variant (Jackson and Gorovsky 2000). Recently, a Drosophila remodeling complex that harbors a Swr1p homolog was shown to replace damage-induced H2Av-Phos with H2Av (Kusch et al 2004).…”

Constitutive Expression Exposes Functional Redundancy between the Arabidopsis Histone H2A Gene HTA1 and Other H2A Gene Family Members

“…Another histone H2A variant, H2A.Z, was first identified by West and Bonner (1980) and is highly conserved throughout evolution. H2A.Z proteins are nonuniformly spread among chromatin (Leach et al, 2000), and they may confer properties distinct from other H2A variants upon the organism (Iouzalen et al, 1996;Jackson and Gorovsky, 2000;Santisteban et al, 2000;Fan et al, 2002). Recently, this histone variant has been implicated in preventing the spread of silent heterochromatin into euchromatic regions of the genome (Mizuguchi et al, 2004).…”