RESUMO
Zinc finger protein ZBTB20 is a novel member of the ZBTB zinc finger protein family and shares closest homology with BCL-6 and PLZF. Recent studies on genetically modified mice and patient cohort have revealed that ZBTB20 plays indispensable roles in multiple organs and systems, including the nervous system, liver, pancreatic islets, and immune system. ZBTB20 is an essential regulatory factor in a variety of physiological processes, such as ontogenesis, pain sensation, learning and memory, as well as glucose and lipid metabolism. Meanwhile, recent researches have also showed a close relationship between the abnormality or dysfunction of ZBTB20 and pathophysiological procedures of diseases, such as maldevelopment, mental retardation, tumors and metabolic disorders. As a key repressor governing AFP gene transcription, ZBTB20 exerts a great influence on the gene inactivation of liver AFP after birth and is closely related to the prognosis of hepatocellular carcinogenesis. In humans, the deletion of ZBTB20 is detected in diverse tumors and its point mutation leads to Primrose syndrome. This review summarizes the current knowledge concerning the biological functions of ZBTB20.
RESUMO
Zinc finger proteins interact via their individual fingers to three base pair subsites on the target DNA. The four key residue positions −1, 2, 3 and 6 on the alpha-helix of the zinc fingers have hydrogen bond interactions with the DNA. Mutating these key residues enables generation of a plethora of combinatorial possibilities that can bind to any DNA stretch of interest. Exploiting the binding specificity and affinity of the interaction between the zinc fingers and the respective DNA can help to generate engineered zinc fingers for therapeutic purposes involving genome targeting. Exploring the structure–function relationships of the existing zinc finger–DNA complexes can aid in predicting the probable zinc fingers that could bind to any target DNA. Computational tools ease the prediction of such engineered zinc fingers by effectively utilizing information from the available experimental data. A study of literature reveals many approaches for predicting DNA-binding specificity in zinc finger proteins. However, an alternative approach that looks into the physico-chemical properties of these complexes would do away with the difficulties of designing unbiased zinc fingers with the desired affinity and specificity. We present a physico-chemical approach that exploits the relative strengths of hydrogen bonding between the target DNA and all combinatorially possible zinc fingers to select the most optimum zinc finger protein candidate.