Griffith, in his 1928 experiments, demonstrated that bacterial strains could be genetically transformed. the evidence that dna was the "transforming principle" responsible for this phenomenon came later. what was the key experiment that avery, maccleod, and mccarty performed to prove that dna was responsible for the genetic change from rough cells into smooth cells?

Griffith's experiment worked with two types of pneumococcal bacteria (a rough type and a smooth type) and identified that a "transforming principle"  could transform them from one type to another.

At first, bacteriologists suspected the transforming factor was a protein. The "transforming principle" could be precipitated with alcohol, which showed that it was not a carbohydrate. But Avery and McCarty observed that proteases (enzymes that degrade proteins) did not destroy the transforming principle. Neither did lipases (enzymes that digest lipids). Later they found that the transforming substance was made of nucleic acids but ribonuclease (which digests RNA) did not inactivate the substance. By this method, they were able to obtain small amounts of highly purified transforming principle, which they could then analyze through other tests to determine its identity, which corresponded to DNA.

this protocol provides a detailed procedure for chromatin immunoprecipitation (chip) to study the dna-protein interactions.