The different ways in which histones can affect chromatin metabolism constitute what has been defined as the ‘histone language’ which is based on a ‘histone code’. Such code results from the combination of histone posttranslational modifications and the specialization imparted to chromatin by the PI-103 exchange of canonical histones by specialized histone variants. Each histone family encompasses a set of minoritary variants, in addition to the main group of canonical proteins, all of them being amenable for PTMs. Among core histones, the H2A family is of great interest due to the high diversity of specialized variants it displays, including proteins involved in critical cellular processes. Indeed, two H2A variants stand out regarding their functional relevance: on one hand, the histone H2A.X is involved in apoptosis, meiosis and replication through its role in the maintenance of genome integrity. Upon DNA DoubleStrand Breaks, H2A.X histones of extensive regions flanking a damaged site become reversibly phosphorylated at their C-terminal SQEY motif creating the so-called ‘H2A.X foci’. This mechanism promotes the dynamic remodeling of chromatin, constituting the primary signal activating the mechanism of DNA DSB repair within the cell nucleus.
On the other hand, histone H2A.Z plays critical roles in gene regulation as well as in the establishment of chromatin boundaries. Furthermore, different reports have directly or indirectly suggested the participation of H2A.Z in the maintenance of genome integrity. For instance, the exchange of c-H2A.X with H2A.Z seems to facilitate the recruitment of DNA repair factors and checkpoint factors. The interest in the study of this variant is thus reliant on its relevance for cell viability as well as on the controversy raised by its apparently dual function in regulating gene activation/repression. The rekindling of the interest in chromatin research during the last 20 years has led to a careful characterization of chromatin structure and dynamics in a wide range of model systems, most notably mammals. However, detailed studies on this matter are very limited in almost any other group, most notably in the case of protostome animals. Molluscs are of special interest for the study of chromatin within this latter group due to two main reasons: first, histone genes are subject to an intense diversification process within this taxonomic group; and second, bivalve molluscs are sentinel organisms widely used in the biomonitoring of pollution in the marine environment, encompassing outstanding economic relevance for the aquaculture industry.
Within this frame, the close connection between the genotoxic effect of different pollutants in the marine environment and the role played by H2A.X and H2A.Z variants in the maintenance of genome integrity opens up a very interesting research pipeline with dual benefits: first, to shed light on the mechanisms underlying chromatin metabolism and dynamics in molluscs; and second, to develop quick and efficient chromatin-based genotoxicity tests in pollution biomonitoring programs. In the present work we identify for the first time the presence of functionally differentiated histone H2A.X and H2A.Z variants in the mussel Mytilus galloprovincialis, a marine mollusc widely used in biomonitoring programs.