Histone variants are non-allelic protein isoforms that play key roles in diversifying chromatin structure. The known number of such variants has greatly increased in recent years, but the lack of naming conventions for them has led to a variety of naming styles, multiple synonyms and misleading homographs that obscure variant relationships and complicate database searches. We propose here a unified nomenclature for variants of all five classes of histones that uses consistent but flexible naming conventions to produce names that are informative and readily searchable. The nomenclature builds on historical usage and incorporates phylogenetic relationships, which are strong predictors of structure and function. A key feature is the consistent use of punctuation to represent phylogenetic divergence, making explicit the relationships among variant subtypes that have previously been implicit or unclear. We recommend that by default new histone variants be named with organism-specific paralog-number suffixes that lack phylogenetic implication, while letter suffixes be reserved for structurally distinct clades of variants. For clarity and searchability, we encourage the use of descriptors that are separate from the phylogeny-based variant name to indicate developmental and other properties of variants that may be independent of structure.

A yeast gene has been identified that encodes a novel, evolutionarily conserved N ␣ -acetyltransferase responsible for acetylation of the N-terminal residues of histones H4 and H2A. The gene has been named NAT4. Recombinant Nat4 protein acetylated a peptide corresponding to the N-terminal tail of H4, but not an H3 peptide nor the peptide adrenocorticotropin. H4 and H2A are N-terminally acetylated in all species from yeast to mammals and hence blocked from sequencing by Edman degradation. In contrast, H4 and H2A purified from a nat4 mutant were unacetylated and could be sequenced. Analysis of yeast histones by acid-urea gel electrophoresis showed that all the H4 and H2A from the mutant migrated more rapidly than the same histones from a wild type strain, consistent with the histones from the mutant having one extra positive charge due to one less acetylated amino group. A comparison of yeast proteins from wild type and a nat4 mutant by two-dimensional gel electrophoresis showed no evidence that other yeast proteins are substrates of this acetyltransferase. Thus, Nat4 may be dedicated specifically to the N-terminal acetylation of histones H4 and H2A. Surprisingly, nat4 mutants grow at a normal rate and have no readily observable phenotypes.Eukaryotic proteins are subject to two cotranslational modifications as the nascent polypeptides emerge from the ribosome, methionine cleavage by methionine aminopeptidase, and acetylation of the ␣-amino group of the N-terminal amino acid (1). Removal of the methionine occurs only if the second amino acid is a small one such as serine, alanine, or glycine. Acetylation of the ␣-amino group on either methionine, or on the N-terminal residue resulting from methionine cleavage, occurs in the great majority of (but not all) eukaryotic proteins, and is accomplished by one of several N ␣ -acetyltransferases (NATs) 1 (1). A number of years ago we identified the genes for a yeast NAT, now called NatA, that consists of two subunits, Ard1 and Nat1 (2). Subsequent work showed that NatA was responsible for the acetylation of many, but not all, yeast proteins beginning with small residues such as serine, alanine, or glycine (2-5). Yeast ard1 and nat1 mutants are viable and the many proteins that are no longer N-terminally acetylated in the mutant strains are as stable as they are in a wild type strain (2). Thus, there is no evidence that N-terminal acetylation serves to protect proteins from degradation in yeast.Ard1 protein has an acetyl-CoA binding motif found in members of the GNAT superfamily, enzymes that acetylate amino groups on proteins and other molecules (6). Thus, Ard1 is very likely to be the catalytic subunit of NatA. Two other NATs have been identified in yeast, called NatB and NatC, with catalytic subunits Nat3 and Mak3, respectively (4, 7). NatB and NatC both acetylate proteins with N-terminal methionine residues, although they have different specificities dictated by the nature of the subsequent amino acids (4).Histone H4 is a highly conserved protein with an N-terminal serin...

Histone acetylation, discovered more than 40 years ago, is a reversible modification of lysines within the amino-terminal domain of core histones. Amino-terminal histone domains contribute to the compaction of genes into repressed chromatin fibers. It is thought that their acetylation causes localized relaxation of chromatin as a necessary but not sufficient condition for processes that repackage DNA such as transcription, replication, repair, recombination, and sperm formation. While increased histone acetylation enhances gene transcription and loss of acetylation represses and silences genes, the function of the rapid continuous or repetitive acetylation and deacetylation reactions with half-lives of just a few minutes remains unknown. Thirty years of in vivo measurements of acetylation turnover and rates of change in histone modification levels have been reviewed to identify common chromatin characteristics measured by distinct protocols. It has now become possible to look across a wider spectrum of organisms than ever before and identify common features. The rapid turnover rates in transcriptionally active and competent chromatin are one such feature. While ubiquitously observed, we still do not know whether turnover itself is linked to chromatin transcription beyond its contribution to rapid changes towards hyper- or hypoacetylation of nucleosomes. However, recent experiments suggest that turnover may be linked directly to steps in gene transcription, interacting with nucleosome remodeling complexes.

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Histone Lys methylation plays an important role in determining chromatin states and is mostly catalyzed by SET domaincontaining proteins. The outcome, transcriptional repression or activation, depends on the methylated histone residue, the degree of methylation, and the chromatin context. Dimethylation or trimethylation of histone H3 Lys 4 (H3K4me2 or H3K4me3) has been correlated with transcriptionally competent/active genes. However, H3K4 methylation has also been implicated in gene silencing. This dualistic nature of the H3K4 methyl mark has thus far remained unresolved. In the green alga Chlamydomonas reinhardtii, Mut11p, related to a subunit of trithorax-like methyltransferase complexes, is required for transcriptional silencing. Here, we show that Mut11p interacts with conserved components of H3K4 methyltransferase machineries, and an affinity-purified Mut11p complex(es) methylates histones H3, H2A, and H4. Moreover, a Mut11 mutant showed global loss of monomethylated H3K4 (H3K4me1) and an increase in dimethylated H3K4. By chromatin immunoprecipitation analysis, this strain also displayed substantial reduction in H3K4me1 and enrichment in H3K4me2 associated with transcriptionally derepressed genes, transgenes, and retrotransposons. RNA interference-mediated suppression of Set1, encoding an H3K4 methyltransferase, induced similar phenotypes, but of lower magnitude, and no detectable increase in H3K4me2. Together, our results suggest functional differentiation between dimethyl H3K4 and monomethyl H3K4, with the latter operating as an epigenetic mark for repressed euchromatin.