OUP accepted manuscript

Abstract

In this work, we developed a database WERAM (http://weram.biocuckoo.org/) for histone acetyltransferases, histone deacetylases, histone methyltransferases, histone demethylases and acetyl- or methyl-binding proteins, which catalyze, remove and recognize histone acetylation and methylation sites as ‘writers’, ‘erasers’ and ‘readers’, and synergistically determine the ‘histone code’. From the scientific literature, we totally collected over 580 experimentally identified histone regulators from eight model organisms, including Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Schizosaccharomyces pombe and Saccharomyces cerevisiae. We also collected ∼900 site-specific regulator-histone relations from the eight species. According to the experimental evidence, known histone regulators were classified into distinct families. To computationally detect more proteins in eukaryotes, we constructed hidden Markov model (HMM) profiles for histone regulator families. For families without HMM profiles, we also conducted orthologous searches. Totally, WERAM database contained more than 20 thousand non-redundant histone regulators from 148 eukaryotes. The detailed annotations and classification information of histone regulators were provided, together with site-specific histone substrates if available.

Epigenetic Modulation of Stem Cells in Neurodevelopment: The Role of Methylation and Acetylation

“…Over 580 histone regulators from eight model organisms classified into distinct families have been collected in a large database 1 (Xu et al, 2017 ). Examples of some compounds belonging to these three groups are presented in Figure 3 .…”

CRISPR-based reagents to study the influence of the epigenome on gene expression

“…These domains include chromodomains which recognize methylated histones, bromodomains which recognize acetylated histone, plant homeodomain (PHD) fingers, TUDOR and WD40 domains (reviewed in 39 ), demonstrating that both reader and writer functionality can reside within the same protein. In addition, histone and DNA‐modifying proteins assemble into multi‐protein complexes such as Complex of Proteins Associated with Set1 (COMPASS), SAGA and polycomb.…”

Focused conformational sampling in proteins

“…Bromodomains are not expected to propagate signals allosterically as they are primarily competitive binders and help in the recruitment and assembly of complexes that regulate transcription and/or modify the histone code. 49,[73][74][75] In general, however, spatial couplings can and will be exposed by PIGS between different parts of a system, e.g., two adjacent monomers in an aggregate. 76 This suggests to us that PIGS can be used precisely to discover the presence (or lack) of allosteric effects, which are known to be difficult to predict and/or simulate.…”