Histone variant innovation in a rapidly evolving chordate lineage

Abstract

BackgroundHistone variants alter the composition of nucleosomes and play crucial roles in transcription, chromosome segregation, DNA repair, and sperm compaction. Modification of metazoan histone variant lineages occurs on a background of genome architecture that shows global similarities from sponges to vertebrates, but the urochordate, Oikopleura dioica, a member of the sister group to vertebrates, exhibits profound modification of this ancestral architecture.ResultsWe show that a histone complement of 47 gene loci encodes 31 histone variants, grouped in distinct sets of developmental expression profiles throughout the life cycle. A particularly diverse array of 15 male-specific histone variants was uncovered, including a testes-specific H4t, the first metazoan H4 sequence variant reported. Universal histone variants H3.3, CenH3, and H2A.Z are present but O. dioica lacks homologs of macroH2A and H2AX. The genome encodes many H2A and H2B variants and the repertoire of H2A.Z isoforms is expanded through alternative splicing, incrementally regulating the number of acetylatable lysine residues in the functionally important N-terminal "charge patch". Mass spectrometry identified 40 acetylation, methylation and ubiquitylation posttranslational modifications (PTMs) and showed that hallmark PTMs of "active" and "repressive" chromatin were present in O. dioica. No obvious reduction in silent heterochromatic marks was observed despite high gene density in this extraordinarily compacted chordate genome.ConclusionsThese results show that histone gene complements and their organization differ considerably even over modest phylogenetic distances. Substantial innovation among all core and linker histone variants has evolved in concert with adaptation of specific life history traits in this rapidly evolving chordate lineage.

Sex-specific chromatin landscapes in an ultra-compact chordate genome

“…S10). It is interesting, therefore, to note that 3 testis-specific H3t variants have substantial modification of the Dot1 recognition site for H3K79 methylation [33]. Repressed TF, ZF and homeodomain (HD) genes, particularly in the testis, had an unusual signature: strong enrichment for H4ac that resulted in assignment to state #15 (Figs.…”

“…A comprehensive developmental transcriptome for O. dioica has been assembled and includes ovary and testes samples [32]. The full histone complement and associated PTMs have also been characterized, showing conservation of histone variants and a histone modification repertoire comparable to vertebrates [33]. …”

Histone H2A variants in nucleosomes and chromatin: more or less stable?

“…For example, H4 is one of the most slowly evolving eukaryotic proteins (23), with variants only described in tetrahymena (24), trypanosomes (25) and the urochordate Oikopleura dioica (26). The H2A family, on the other hand, contains a plethora of variants with some ‘universal variants’ found in almost all organisms, namely H2A.Z and H2A.X (7).…”

MS_HistoneDB, a manually curated resource for proteomic analysis of human and mouse histones

“…Some of these variants are specifically expressed during sperm differentiation and are annotated TS for testis-specific [24–26]. Altogether, histone variants have been described for H3, H2A, H2B and H1; H4 is the only histone for which no variant has been identified in mammals, but some organisms, such as the urochordate Oikopleura dioica , ciliates and trypanosomes, have evolved H4 variants [10, 27–29]. …”