Zinc finger protein biology
Recent observations indicate that genes encoding for Krüppel associated box (KRAB) zinc finger (ZNF) proteins, an evolutionarily conserved family of transcriptional regulators, are expressed predominantly in testis and the foetal brain. Some of their known functions include transcriptional repression of RNA polymerase I, II, and III promoters, binding and splicing of RNA, and control of nucleolus function. The EU-funded KRAB-ZNF (KRAB zinc finger gene biology in evolution and disease) project wished to elucidate the functions of KRAB ZNF genes in evolution and diseases. In this context, research teams combined their expertise in KRAB-ZNF gene biology and correlated protein expression and function to longevity, fertility and cognition in various species ranging from birds to mammals. They also analysed the role of SNPs of brain-related genes in social behaviour of primates and investigated how KRAB-ZNF target proteins may be implicated in human pathology. Following comparison with existing knowledge, researchers further analysed the experimental data in conjunction with that obtained following perturbation by small molecules, and assembled it in comprehensive open access databases. Besides elucidating KRAB-ZNF gene functions in primate evolution and ontogenesis, the consortium also generated important information on their expression patterns in human cancers and normal human tissues. Furthermore, the generated knowledge could serve as the basis for studies in induced pluripotent stem cells. This would help delineate the function of different KRAB-ZNF proteins in cell differentiation and organogenesis. Overall, given the regulatory role of KRAB-ZNF proteins, elucidating their expression during evolution alongside their distinct cellular functions will unveil novel pathways for key processes in health and disease.
Keywords
Evolution, KRAB zinc finger proteins, longevity, cognition, cancer
