Pre-messenger RNA splicing is carried out by a large ribonucleoprotein complex 
called the spliceosome. Despite the striking evolutionary conservation of the 
spliceosomal components and their functions, controversy persists about the 
relative importance of splicing in Saccharomyces cerevisiae-particularly given 
the paucity of intron-containing genes in yeast. Here we show that splicing of 
one pre-messenger RNA, SUS1, a component of the histone H2B ubiquitin protease 
machinery, is essential for establishing the proper modification state of 
chromatin. One protein complex that is intimately involved in pre-mRNA splicing, 
the yeast cap-binding complex, appears to be particularly important, as 
evidenced by its extensive and unique genetic interactions with enzymes that 
catalyze histone H2B ubiquitination. Microarray studies show that cap binding 
complex (CBC) deletion has a global effect on gene expression, and for 
approximately 20% of these genes, this effect is suppressed when ubiquitination 
of histone H2B is eliminated. Consistent with this finding of histone H2B 
dependent effects on gene expression, deletion of the yeast cap binding complex 
leads to overubiquitination of histone H2B. A key component of the 
ubiquitin-protease module of the SAGA complex, Sus1, is encoded by a gene that 
contains two introns and is misspliced when the CBC is deleted, leading to 
destabilization of the ubiquitin protease complex and defective modulation of 
cellular H2B levels. These data demonstrate that pre-mRNA splicing plays a 
critical role in histone H2B ubiquitination and that the CBC in particular helps 
to establish the proper state of chromatin and proper expression of genes that 
are regulated at the level of histone H2B ubiquitination.