AMINO-ACID SUBSTITUTIONS IN THE STRUCTURED DOMAINS OF HISTONES H3 ANDH4 PARTIALLY RELIEVE THE REQUIREMENT OF THE YEAST SWI SNF COMPLEX FORTRANSCRIPTION/

Transcription of many yeast genes requires the SWI/SNF regulatory comp lex. Prior studies show that reduced transcription of the HO gene in s wi and snf mutants is partially relieved by mutations in the SIN1 and SIN2 genes. Here we show that SIN2 is identical to HHT1, one of the tw o genes coding for histone H3, and that mutations in either can result in a Sin(-) phenotype. These mutations are partially dominant to wild type and cause amino acid substitutions in three conserved positions in the structured domain of histone H3. We have also identified partia lly dominant sin mutations that affect two conserved positions in the histone-fold domain of histone H4. Three sin mutations affect surface residues proposed to interact with DNA and may reduce affinity of DNA for the histone octamer. Two sin mutations affect residues at or near interfaces between (H2A-H2B) dimer and (H3-H4)(2) tetramer subunits of the histone octamer and may affect nucleosome stability or conformati on. The ability of mutations affecting the structure of the histone oc tamer to relieve the need for SWI and SNF products supports the propos al that the SWI/SNF complex stimulates transcription by altering chrom atin structure and can account for the apparent conservation of SWI an d SNF proteins in eukaryotes other than yeast.