This is not my theory but thought I'd share
Could Shisui have used his Mangekyo Sharingan's Kotoamatsukami on Itachi before he died to cause him to kill their clan? The Kotoamatsukami allows the user to plant false memories, making the victim believe they are doing things of their own free will. We know that Shisui loved the village more than his clan, and his final words were about protecting Konohana against the Uchihas. Even though it is true that Shisui and Itachi were like brothers and trusted each other; this would be Shisui's final act so why would he not use all his powers to ensure the village was protected?
Or could it be Danzo's doing ?