We describe here a simple procedure for greatly reducing contamination of 
nuclear extracts by naturally biotinylated cytoplasmic carboxylases, which 
represent a major source of non-specific background when employing BirA-mediated 
biotinylation tagging for the purification and characterization of nuclear 
protein complexes by mass spectrometry. We show that the use of 0.5% of the 
non-ionic detergent Nonidet-40 (NP-40) during cell lysis and nuclei isolation is 
sufficient to practically eliminate contamination of nuclear extracts by 
carboxylases and to greatly reduce background signals in downstream mass 
spectrometric analyses.