Comprehensive Database of Histone Proteins and Epigenetic Drugs

In HISTome2, the information on histone proteins, PTMs and modifying enzymes in human, rat and mouse was manually curated from NCBI, uniport, gene-cards, histone DB2.0, and Talbert et al. [52 –56 (link)]. The methodology for data mining for ‘detailed information page’ was modified from the earlier version (HIstome) because for chromosomal location, URL was no longer available and the Unigene database will be discontinued shortly. Therefore, UniProt accession ID was provided for all the entries as it is the most comprehensive protein database which provides detailed functional information for the proteins. Further, gene-related information such as name, symbol, and GeneID was acquired from HGNC [57 ], RGD [58 (link)], and MGI [59 (link)] for human, rat, and mouse, respectively. Gene, transcript, and protein-related information were obtained from NCBI, while EC number was fetched from EC-PDB [60 ]. Promoter sequences for different histones and modifying enzymes were obtained from EPD [61 ]. The PubMed link was provided to each entry with pre-embedded aliases in keywords to fetch updated information and to exclude non-specific searches. However, if the PubMed search did not display any literature, a specific PMID reference link is provided. An additional hyperlink was provided to all the entries for humans to retrieve TCGA mRNA expression from FireBrowse [33 ] and mIR targets from TargetScan [34 ].
A new component in the database, EpiDrug is added to highlight its importance in the field of epigenetics and potential in the treatment of different diseases. The information on the epidrugs was retrieved from PubMed, PubMed Central, and Google scholar, using different searches related to DNA methylation and histone-modifying enzymes like DNA methyltransferase inhibitors, histone acetyltransferase inhibitors, histone deacetylase inhibitors, histone methyltransferase inhibitors, histone acetyltransferase inhibitors, histone demethylase inhibitors, inhibitors of proteins binding to methylated histones, protein arginine deiminases inhibitors, poly (ADP-ribose) polymerase inhibitors, inhibitors of bromodomain (BRD) and extra-terminal domain (BET) family of proteins, and inhibitors of ubiquitinases and deubiquitinases. The information on synonyms, molecular formula, molecular weight, IUPAC, InChl, smiles, and 2D structures of epidrugs are obtained from the PubChem compound database [62 (link)]. The list of biological assays that have been performed on these chemical compounds to determine the chemical toxicity and bioactivity is acquired from the PubChem BioAssay database [2 (link)]. The information on the FDA status and ongoing clinical trials is fetched from ClinicalTrial.gov [63 ].