I always read that for native ChIP (N-ChIP) you can use micrococcal nuclease to generate fragments but for formaldehyde crosslinked ChIP (X-ChIP) one should sonicate to shear because the micrococcal nuclease sites could be blocked. N-ChIP should be perfect for IP of histones which is what I'm interesting in doing right now, but I'm looking for a simplified protocol and I like the idea of shearing with a water bath sonicator such as the Bioruptor.

So, my question: is there a reason why one cannot sonicate native chromatin? Will the histones detach under these conditions if not fixed first?

You are probably right. The sonication would break up the bonds between chromatin and associated proteins. However, I am unsure whether histones would detach from chromatin by sonication. A good review in Biotechniques
BioTechniques

I would not recommend a sonicating water bath since the energy is not concentrated enough to give you necessary shearing in the minimum of time nor will the sample be cooled.

Hello, have you finally founded a protocol for N-ChIP using the sonication for shearing the chromatin?
Thanks,

Sadly, no progress on using sonication with N-ChIP. Although I haven't been actively pursuing it, I'm just trying to get X-ChIP to work reliably!

You should use a high intensity water bath accessory (cup horn) with much higher power density due to the special form of the cup horn itsself.
Use a BRANSON SONIFIER using a cuphorn HIGH INTENSITY (only available with BRANSON units!! Must be a HIGH INTENSITY!!) ) plus an added cooling device (including right cooling fluid) have best performance.
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