ChromoHub: a data hub for navigators of chromatin-mediated signalling

Abstract

Summary: The rapidly increasing research activity focused on chromatin-mediated regulation of epigenetic mechanisms is generating waves of data on writers, readers and erasers of the histone code, such as protein methyltransferases, bromodomains or histone deacetylases. To make these data easily accessible to communities of research scientists coming from diverse horizons, we have created ChromoHub, an online resource where users can map on phylogenetic trees disease associations, protein structures, chemical inhibitors, histone substrates, chromosomal aberrations and other types of data extracted from public repositories and the published literature. The interface can be used to define the structural or chemical coverage of a protein family, highlight domain architectures, interrogate disease relevance or zoom in on specific genes for more detailed information. This open-access resource should serve as a hub for cell biologists, medicinal chemists, structural biologists and other navigators that explore the biology of chromatin signalling.Availability: http://www.thesgc.org/chromohub/.Contact: matthieu.schapira@utoronto.caSupplementary Information: Supplementary data are available at Bioinformatics online.

Histone Recognition by Human Malignant Brain Tumor Domains

“…[18][19][20][21][22][23][24][25][26] To test if this feature is universal among human MBT proteins, we constructed a phylogenetic tree 29 to show similarity between individual MBT repeats (Fig. 1b).…”

“…(b) Phylogenetic tree of the individual human MBT domains generated using ChromoHub. 29 The name of the protein is followed by the underscore and the sequential MBT domain numbering starting from the N-terminus. Indicated in red are MBT domains that have functional aromatic cages.…”

The bromodomain: From epigenome reader to druggable target

“…A query of ChEpiMod (version 2014.02.03) shows that the BrDs with the most compounds developed (with potency better than 10 μM) are BRD4-BrD1 (196 compounds), BRD4-BrD2 (119), CBP BrD (97 compounds), PCAF/KAT2B BrD (60 compounds), EP300 BrD (26 compounds), and BRD2-BrD1 (12 compounds). ChromoHub [77, 78] is another related database for epigenome reader, writer and eraser domains. Although it is not focused on chemical modulators or their molecular interactions with these domains, ChromoHub is a valuable resource for exploring epigenetic mechanisms concerning cancer genomics.…”

Targeting Epigenetics: An Epicenter of Oncology Drug Discovery?

“…The discovery of these protein families has generated substantial interest from biotech and pharmaceutical industry to develop novel, target-selective epigenetic modulators. There are over 60 family members in the HMT class to specifically methylate lysine or arginine residues (3,11). A small molecule, BIX-01294 was first identified as selective G9a inhibitor during a chemical screen (12).…”

“…The H3K4 demethylase RBP2 contains an ARID domain which binds to a specific DNA sequence (CCGCCC). Many reader domains exist, including the Bromo domain which reads acetylated lysines; the CXXC domain which reads nonmethyl CpG dinucleotides; the MBD domain which reads methyl-CpG dinucleotide and the Chromo/Phd/Tudor/WD40 domains which read methylated lysine (3,11). It was soon recognized that inhibition of reader domain binding to specific epigenetics marks can be an attractive target modulation approach to treat cancers.…”