Two meters of DNA are folded within each cell nucleus. Histone proteins associate to form the nucleosome, which is key to the functionality of the genome and the regulation of transcription. This nucleosomal structure is super-organized at different scales, the most compact one being the metaphase chromosome. While genome sequencing has become a routine act, proteomic analyzes of the content of the cell nucleus, especially histones, remain complicated.

A wide diversity of histones has been described, with more than 80 isoforms and variants. Some have different sequences, which may result from the addition of an entire macromolecular domain. Other forms of histones only vary by a few amino acids. They have been described over the years across different species. In 2012, a first collective effort led to the creation of a nomenclature based on histone genes. This work was unfortunately not adapted to proteomic analyzes. Indeed, some isoforms have been grouped within the same functional family, for example "canonical H2B", while they show variations of sequences (although minor) which are detected by mass spectrometry. At the end, this first nomenclature led to the assignment of hazardous names and homonymies which are incompatible with proteomic analyzes.
In collaboration, we have tackled this issue in humans and mice. We gathered and organized more than 1,700 entries in two databases. They regroup 168 unique proteins and some were renamed to clarify proteomic analyzes. Two ready-to-use databases are now proposed to the scientific community and can be directly used for proteomic analyzes of human and mouse histones. A first set of experiments notably confirmed the expression of several histone variants of mice, variants whose existence was previously only inferred by homology.