Is it ever useful to do a non-specific antibody first, then a specific antibody?
In general it is not useful. It is certainly possible that this can be done, but the more purification steps you add to your method, the less enriched DNA you will end up as a result. This may be desirable in certain circumstances, but it shouldn’t be the default for ChIP. There’s the added issue of being unable to completely remove the non-specific antibody from the reaction which may increase the number of reads going to non-specific sites rather than decreasing it. – answered by Tovah Markowitz, Paul Schaughency, Vishal Koparde
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