You are a U.K. publication so you should use theregister.co.uk and if you want to have targeted content simply do as the BBC do at news.bbc.co.uk and allow users to choose between a U.K. or International edition.
I think you are big enough and have enough readers now that it doesn't matter. The BBC don't have a .com address and they have millions of readers from all around the world. Why do you need a .com address? Are you just worried that our American cousins will think less of a .co.uk domain than a .com domain? That's just silly and the BBC is proof that if your content is good and something that people want to read then the domain doesn't really matter.
/Steve (from U.K. but currently residing in Västerås, Sweden)