HIstome

Abstract: The role of histone modifications in the development and progression of cancer remains unclear. Here, we gave an investigation of the relationship between the various histone modifications and the risk prediction of the biochemical recurrence after radical prostatectomy (RP). Histone 3 lysine 4 dimethylation (H3K4diMe), trimethylation (H3K4triMe), lysine 36 trimethylation (H3K36triMe), histone 4 lysine 20 trimethylation (H4K20triMe) and acetylation of histome 3 lysine 9 (H3K9Ac) were evaluated using immnuohistochemistry coupled with the tissue microarray technique in 169 primary prostatectomy tissue samples. Recursive partitioning analysis (RPA) was used to analyze the data. Through global histone modification analysis in patients who underwent radical prostatectomy, we found that H3K4triMe can predict the risk of the biochemical recurrence for the low grade prostate cancer (Gleason score ≤ 6) after RP. In the case of high grade prostate cancer (Gleason score ≥ 7), H4K20triMe and H3K9Ac accompanying with the pre-operation prostate-specific antigen (PSA) level could also predict the risk of the biochemical recurrence after RP. In combination with the Gleason score and pre-operation PSA level, the acetylation and methylation of histones H3 and H4 can predict the biochemical recurrence of the prostate cancer following RP.

Abstract: Epigenetics research is progressing in basic, pre-clinical and clinical studies using various model systems. Hence, updating the knowledge and integration of biological data emerging from in silico, in vitro and in vivo studies for different epigenetic factors is essential. Moreover, new drugs are being discovered which target various epigenetic proteins, tested in pre-clinical studies, clinical trials and approved by the FDA. It brings distinct challenges as well as opportunities to update the existing HIstome database for implementing and applying enormous data for biomedical research. HISTome2 focuses on the sub-classification of histone proteins as variants and isoforms, post-translational modifications (PTMs) and modifying enzymes for humans (Homo sapiens), rat (Rattus norvegicus) and mouse (Mus musculus) on one interface for integrative analysis. It contains 232, 267 and 350 entries for histone proteins (non-canonical/variants and canonical/isoforms), PTMs and modifying enzymes respectively for human, rat, and mouse. Around 200 EpiDrugs for various classes of epigenetic modifiers, their clinical trial status, and pharmacological relevance have been provided in HISTome2. The additional features like ‘Clustal omega’ for multiple sequence alignment, link to ‘FireBrowse’ to visualize TCGA expression data and ‘TargetScanHuman’ for miRNA targets have been included in the database. The information for multiple organisms and EpiDrugs on a common platform will accelerate the understanding and future development of drugs. Overall, HISTome2 has significantly increased the extent and diversity of its content which will serve as a ‘knowledge Infobase’ for biologists, pharmacologists, and clinicians. HISTome2: The HISTone Infobase is freely available on http://www.actrec.gov.in/histome2/ .

Abstract: Histones are abundant nuclear proteins that are essential for the packaging of eukaryotic DNA into chromosomes. Different histone variants, in combination with their modification ‘code’, control regulation of gene expression in diverse cellular processes. Several enzymes that catalyze the addition and removal of multiple histone modifications have been discovered in the past decade, enabling investigations of their role(s) in normal cellular processes and diverse pathological conditions. This sudden influx of data, however, has resulted in need of an updated knowledgebase that compiles, organizes and presents curated scientific information to the user in an easily accessible format. Here, we present HIstome, a browsable, manually curated, relational database that provides information about human histone proteins, their sites of modifications, variants and modifying enzymes. HIstome is a knowledgebase of 55 human histone proteins, 106 distinct sites of their post-translational modifications (PTMs) and 152 histone-modifying enzymes. Entries have been grouped into 5 types of histones, 8 types of post-translational modifications and 14 types of enzymes that catalyze addition and removal of these modifications. The resource will be useful for epigeneticists, pharmacologists and clinicians. HIstome: The Histone Infobase is available online at http://www.iiserpune.ac.in/∼coee/histome/ and http://www.actrec.gov.in/histome/.