CHHM: a Manually Curated Catalogue of Human Histone Modifications Revealing Hotspot Regions and Unique Distribution Patterns

Histone modification is one of the key elements in epigenetic control and plays important roles in regulation of biological processes and disease development. Currently, records of human histone modifications with various levels of confidence in evidence are scattered in various knowledgebases and databases. In the present study, a curated catalogue of human histone modifications, CHHM, was obtained by manual retrieval, evidence assessment, and integration of modification records from 10 knowledgebases/databases and 3 complementary articles. CHHM contains 6612 nonredundant modification entries covering 31 types of modifications (including 9 types of emerging modifications) and 2 types of histone-DNA crosslinks, that were identified in 11 H1 variants, 21 H2A variants, 21 H2B variants, 9 H3 variants, and 2 H4 variants. For ease of visualization and accessibility, modification entries are presented with aligned protein sequences in an Excel file. Confidence level in evidence is provided for each entry. Acylation modifications contribute to the highest number of modification entries in CHHM. This supports that cellular metabolic status plays a very important role in epigenetic control. CHHM reveals modification hotspot regions and uneven distribution of the modification entries across the histone families. Such uneven distribution may suggest that a particular histone family is more susceptible to certain types of modifications. CHHM not only serves as an important and user-friendly resource for biomedical and clinical researches involving histone modifications and transcriptional regulation, but also provides new insights for basic researches in the mechanism of human histone modifications and epigenetic control.