Should we always use histone markers just to see if our sequencing is working for our samples?
No, there is no reason to start with a histone marker just to see if sequencing is working for your samples. If you are worried about a specific cell type for any reason or this is your first time making a ChIP-seq library, it is beneficial to do a positive control experiment but that does not need to be a histone marker. In fact, an IP of a generic histone like H3 can actually be difficult to differentiate from an input sometimes and may make it difficult for you to feel confident in the results. – answered by Tovah Markowitz, Paul Schaughency, Vishal Koparde.
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