A global view of all core histones in yeast is provided by tandem mass 
spectrometry of intact histones H2A, H2B, H4, and H3. This allowed detailed 
characterization of >50 distinct histone forms and their semiquantitative 
assessment in the deletion mutants gcn5Delta, spt7Delta, ahc1Delta, and 
rtg2Delta, affecting the chromatin remodeling complexes SAGA, SLIK, and ADA. The 
"top down" mass spectrometry approach detected dramatic decreases in acetylation 
on H3 and H2B in gcn5Delta cells versus wild type. For H3 in wild type cells, 
tandem mass spectrometry revealed a direct correlation between increases of 
Lys(4) trimethylation and the 0, 1, 2, and 3 acetylation states of histone H3. 
The results show a wide swing from 10 to 80% Lys(4) trimethylation levels on 
those H3 tails harboring 0 or 3 acetylations, respectively. Reciprocity between 
these chromatin marks was apparent, since gcn5Delta cells showed a 30% decrease 
in trimethylation levels on Lys(4) in addition to a decrease of acetylation 
levels on H3 in bulk chromatin. Deletion of Set1, the Lys(4) methyltransferase, 
was associated with the linked disappearance of both Lys(4) methylation and 
Lys(14) and Lys(18) or Lys(23) acetylation on H3. In sum, we have defined the 
"basis set" of histone forms present in yeast chromatin using a current mass 
spectrometric approach that both quickly profiles global changes and directly 
probes the connectivity of modifications on the same histone.