More than 700 human genes encode proteins with zinc fingers, evolution’s answer to a built-in genetic toolkit. These long, finger-like proteins — single or clusters of eight or more — hinge on a zinc atom, and bind to specific nucleotide sequences (combinations of ATCG in DNA or AUCG in RNA).
Zinc fingers can carry out a number of vital functions including gene expression, over large regions of the genome. And they hold promise as a mechanism for delivering corrective treatments for genetic diseases.
But despite their importance, says Jackson Laboratory (JAX) Senior Research Scientist Petko Petkov, Ph.D., “we still lack a comprehensive knowledge on the rules that determine these proteins' binding to DNA, and the existing prediction programs do not perform satisfactorily.”
The National Institute of General Medical Sciences has awarded Petkov a four-year grant totaling $1,385,337 to exploit the new methods he has developed to profile and investigate zinc finger proteins and their binding sites.
“We propose to apply these methods for comprehensive analysis of DNA binding sites of over 20 mouse and human natural protein variants of the recombination regulator PRDM9,” Petkov says, “as well as over 100 other human and mouse zinc finger proteins, which represent different groups of long zinc finger array proteins, and whose binding sites have not been determined previously.
The National Institute of General Medical Sciences: DNA Binding Properties of Zinc Finger Proteins, Grant Number 1R01GM125736-01A1