The role of Ca2+-signaling in the regulation of epigenetic mechanisms

Epigenetic mechanisms regulate multiple cell functions like gene expression and chromatin conformation and stability, and its misregulation could lead to several diseases including cancer. Epigenetic drugs are currently under investigation in a broad range of diseases, but the cellular processes involved in regulating epigenetic mechanisms are not fully understood. Calcium (Ca²⁺) signaling regulates several cellular mechanisms such as proliferation, gene expression, and metabolism, among others. Moreover, Ca²⁺ signaling is also involved in diseases such as neurological disorders, cardiac, and cancer. Evidence indicates that Ca²⁺ signaling and epigenetics are involved in the same cellular functions, which suggests a possible interplay between both mechanisms. Ca²⁺-activated transcription factors regulate the recruitment of chromatin remodeling complexes into their target genes, and Ca²⁺-sensing proteins modulate their activity and intracellular localization. Thus, Ca²⁺ signaling is an important regulator of epigenetic mechanisms. Moreover, Ca²⁺ signaling activates epigenetic mechanisms that in turn regulate genes involved in Ca²⁺ signaling, suggesting possible feedback between both mechanisms. The understanding of how epigenetics are regulated could lead to developing better therapeutical approaches.