A physical basis for quantitative ChIP-sequencing [Methods and Resources]

We report a significant increase in immunoprecipitation of presumed off-target histone PTMs after inhibitor treatment, a trend predicted by the model but contrary to spike-in–based indications. Our work also identifies a sensitivity issue in spike-in normalization that has not been considered in the literature, placing limitations on its utility and trustworthiness. We call our new approach the sans-spike-in method for quantitative ChIP-sequencing (siQ-ChIP). A number of changes in community practice of ChIP-Seq, data reporting, and analysis are motivated by this work.

Source: Journal of Biological Chemistry - November 20, 2020 Category: Chemistry Authors: Bradley M. Dickson, Rochelle L. Tiedemann, Alison A. Chomiak, Evan M. Cornett, Robert M. Vaughan, Scott B. Rothbart Tags: Editors ' Picks Source Type: research