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Be aware that there was a change in join syntax as of MySQL 5.0.12. This may cause some problems as some queries that worked before will need to be rewritten. At the very least there will likely be some applications that need to be updated ( I would guess, seeing as you have 400 domains). I would use caution making this upgrade.
HTH
its almost certain that at least a few sites will break, make sure you let the right people know before you do it, and always keep backups of customer data
you may need to fix tables after the upgrade as well