A NEW CLASS OF HISTONE H2A MUTATIONS IN SACCHAROMYCES-CEREVISIAE CAUSES SPECIFIC TRANSCRIPTIONAL DEFECTS IN-VIVO

Nucleosomes have been shown to repress transcription both in vitro and in vivo. However, the mechanisms by which this repression is overcome are only beginning to be understood. Recent evidence suggests that in the yeast Saccharomyces cerevisiae, many transcriptional activators r equire the SNF/SWI complex to overcome chromatin-mediated repression. We have identified a new class of mutations in the histone H2A-encodin g gene HTA1 that causes transcriptional defects at the SNF/SWI-depende nt gene SUC2. Some of the mutations are semidominant, and most of the predicted amino acid changes are in or near the N- and C-terminal regi ons of histone H2A. A deletion that removes the N-terminal tail of his tone H2A also caused a decrease in SUC2 transcription. Strains carryin g these histone mutations also exhibited defects in activation by LexA -GAI4, a SNF/SWI-dependent activator. However, these H2A mutants are p henotypically distinct from snf/swi mutants. First, not all SNF/SWI-de pendent genes showed transcriptional defects in these histone mutants. Second, a suppressor of snf/swi mutations, spt6, did not suppress the se histone mutations. Finally, unlike in snf/swi mutants, chromatin st ructure at the SUC2 promoter in these H2A mutants was in an active con formation. Thus, these H2A mutations seem to interfere with a transcri ption activation function downstream or independent of the SNF/SWI act ivity. Therefore, they may identify an additional step that is require d to overcome repression by chromatin.