A method to identify and quantify chromatin-associated proteins has been developed and applied to the analysis of changes in chromatin-associated proteins induced by Myc oncoprotein expression in human B lymphocytes. Chromatin-enriched fractions were isolated by differential detergent/salt extraction and analyzed by ICAT reagent labeling, multi-dimensional chromatography and tandem mass spectrometry. Many known chromatin-associated regulatory factors were identified and quantified. The method will be widely applicable to various biological systems and reveal changes in chromatin-associated regulatory factors that underlie biological phenomena.