HistoneDB 2.0: a histone database with variants—an integrated resource to explore histones and their variants

Abstract

Compaction of DNA into chromatin is a characteristic feature of eukaryotic organisms. The core (H2A, H2B, H3, H4) and linker (H1) histone proteins are responsible for this compaction through the formation of nucleosomes and higher order chromatin aggregates. Moreover, histones are intricately involved in chromatin functioning and provide a means for genome dynamic regulation through specific histone variants and histone post-translational modifications. ‘HistoneDB 2.0 – with variants’ is a comprehensive database of histone protein sequences, classified by histone types and variants. All entries in the database are supplemented by rich sequence and structural annotations with many interactive tools to explore and compare sequences of different variants from various organisms. The core of the database is a manually curated set of histone sequences grouped into 30 different variant subsets with variant-specific annotations. The curated set is supplemented by an automatically extracted set of histone sequences from the non-redundant protein database using algorithms trained on the curated set. The interactive web site supports various searching strategies in both datasets: browsing of phylogenetic trees; on-demand generation of multiple sequence alignments with feature annotations; classification of histone-like sequences and browsing of the taxonomic diversity for every histone variant. HistoneDB 2.0 is a resource for the interactive comparative analysis of histone protein sequences and their implications for chromatin function.Database URL: http://www.ncbi.nlm.nih.gov/projects/HistoneDB2.0

Database Resources of the National Center for Biotechnology Information

“…‘HistoneDB 2.0–with variants’ is a new database of histone protein sequences classified by histone types and variants (9). The database contains a manually curated set of histone sequences grouped into 30 different variant subsets with variant-specific annotations.…”

Genetic Polymorphisms Associated with Idiopathic Short Stature and First-Year Response to Growth Hormone Treatment

“…Second, SAP49/SF3B4 inhibits BMP-mediated osteochondral differentiation in vitro by binding to a BMP receptor [56]. The A/major allele at rs11205277 is designated as the “short” allele due to associations with reduced height in earlier studies [5, 54]. Thus, our finding of faster GH-mediated growth in subjects homozygous for this “short” allele may be considered unexpected.…”

“…The involvement of this locus in stature was confirmed in additional studies of Caucasian subjects [5, 53], including a meta-analysis of over 100,000 subjects that identified 180 SNPs explaining about 10% of the variance in adult height [5]. The relevance of rs11205277 for childhood growth, as distinct from adult height, was subsequently revealed in an examination of associations between the original 180 adult-height SNPs and different phases of childhood growth in approximately 8,000 participants from the Avon Longitudinal Study of Parents and Children [54]; rs11205277 was 1 of just 10 SNPs that retained significance after multiplicity adjustment. The G allele at this locus was significantly associated with birth length as part of an allelic score (number of “tall” alleles), although the effect of each contributory allele was small; at age 10 years the G allele contributed up to 0.6 cm of total height.…”

OUP accepted manuscript

“…Thus, the collection of histone modifications together with their cognate regulators has emerged to be a great challenge. Currently, there have been four major databases developed for histones and histone modifications, including HHMD, Hlstome, dbHiMo and HistoneDB (25–28). For example, HHMD collected 43 location-specific histone modifications in humans, focusing on the storage and integration of histone modification datasets (25), while Hlstome contained 55 human histones, 106 site-specific PTMs and 152 histone-modifying enzymes (26).…”

“…The dbHiMo mainly focused on the identification of histone-modifying enzymes in fungi, whereas readers and site-specific histone modifications were not included (27). HistoneDB maintained histone sequences, structural annotations, for the exploration of histones and their variants (28). These data resources mainly focused on the collection of histone sequences and structures, or histone modifications in human and fungi, whereas an integrative database in eukaryotes is still lacking.…”