Monitoring the Nuclear-Cytosolic Shuttling and Phosphorylation Level of Class IIa Histone Deacetylases by Small-Molecule Fluorogenic Probe

Class IIa histone deacetylases (IIa HDACs) have been considered as the key regulators of numerous cellular processes, and related to many diseases included cardiovascular disease, cancer, inflammation, diabetes, neurodegenerative diseases and epigenetic response to drug stimulus. However, the understanding of detailed function of IIa HDACs remain breezing. One reason is that understanding the function not only need detect the expression of IIa HDACs at various condition or stimulus but also determine their distribution, because IIa HDACs can shuttle between nuclear and cytosolic in a phosphorylation-dependent manner and their function was regulated by the shuttling behavior. Hence, we generated a highly specific small-molecule fluorescent probe targeting IIa HDACs (NFP-HDAC). The probe exhibits ultrahigh temporal-spatial resolution and excellent cell penetration capacity, and can accurately monitor the expression, phosphorylation level and distribution of IIa HDACs. This work offers a novel visible tool for the imaging of IIa HDAC related tumor and molecular biology research about IIa HDACs.