Characterization of the histone H2A.Z-1 and H2A.Z-2 isoforms in vertebrates

Deanna Dryhurst,Toyotaka Ishibashi,Michael J Hendzel,Kristie L Rose,Jeffrey Shabanowitz,Donald F Hunt,Darin Mcdonald,Begonia Silva-Moreno,Juan Ausió,Caren C Helbing,José M Eirín-López,Nik Veldhoen

doi:10.1186/1741-7007-7-86

Abstract

BackgroundWithin chromatin, the histone variant H2A.Z plays a role in many diverse nuclear processes including transcription, preventing the spread of heterochromatin and epigenetic transcriptional memory. The molecular mechanisms of how H2A.Z mediates its effects are not entirely understood. However, it is now known that H2A.Z has two protein isoforms in vertebrates, H2A.Z-1 and H2A.Z-2, which are encoded by separate genes and differ by 3 amino acid residues.ResultsWe report that H2A.Z-1 and H2A.Z-2 are expressed across a wide range of human tissues, they are both acetylated at lysine residues within the N-terminal region and they exhibit similar, but nonidentical, distributions within chromatin. Our results suggest that H2A.Z-2 preferentially associates with H3 trimethylated at lysine 4 compared to H2A.Z-1. The phylogenetic analysis of the promoter regions of H2A.Z-1 and H2A.Z-2 indicate that they have evolved separately during vertebrate evolution.ConclusionsOur biochemical, gene expression, and phylogenetic data suggest that the H2A.Z-1 and H2A.Z-2 variants function similarly yet they may have acquired a degree of functional independence.

Highlights

Within chromatin, the histone variant H2A.Z plays a role in many diverse nuclear processes including transcription, preventing the spread of heterochromatin and epigenetic transcriptional memory
The N-terminal tails of H2A.Z-1 and H2A.Z-2 are acetylated in vivo in chicken cells We employed a mass spectrometric approach in order to determine if the N-terminal tail of H2A.Z-1 is acetylated in vivo in a similar way to the recently described acetylation of the same region in H2A.Z-2 [27]
The H2A.Z peptides were analysed by LC-coupled tandem mass spectrometry which enabled sequence determination of the first 19 residues of both H2A.Z-1 (AGGKAGKDSGKTKTKAVSR) and H2A.Z-2

Summary

Introduction

The histone variant H2A.Z plays a role in many diverse nuclear processes including transcription, preventing the spread of heterochromatin and epigenetic transcriptional memory. Histones represent the major protein component of chromatin and most of the synthesis of the canonical forms takes place during S phase of the cell cycle to allow for efficient packaging of the newly replicated DNA. A subset of histone variants is synthesized throughout the cell cycle and can replace canonical histones to specify chromatin domains for specific functions [1,2]. Histone H2A.Z is one such replacement histone variant and while it is very widely studied, its structural and functional roles have proven to be many and diverse and controversial [2,3]

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