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A biotin-labeled DNA probe is designed to target a specific genomic or regulatory region of interest. The labeled probe is subsequently captured by streptavidin-coated magnetic beads via the high-affinity biotin-streptavidin interaction. The immobilized DNA probe is then incubated with total protein extracts, allowing proteins that specifically recognize or bind the target DNA sequence to form a bead-DNA-protein ternary complex. Following stringent washes to remove non-specifically bound contaminants, the captured DNA-protein complexes are eluted under optimized conditions. The eluted proteins are subsequently identified and characterized by Western blot (for validation of known DNA-binding proteins) or mass spectrometry (for unbiased discovery of novel interacting proteins).