Kruger W, Peterson C L, Sil A, Coburn C, Arents G, Moudrianakis E N, Herskowitz I
Department of Biochemistry and Biophysics, University of California, San Francisco, School of Medicine 94143-0448, USA.
Genes Dev. 1995 Nov 15;9(22):2770-9. doi: 10.1101/gad.9.22.2770.
Transcription of many yeast genes requires the SWI/SNF regulatory complex. Prior studies show that reduced transcription of the HO gene in swi 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 two 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 partially 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 conformation. The ability of mutations affecting the structure of the histone octamer to relieve the need for SWI and SNF products supports the proposal that the SWI/SNF complex stimulates transcription by altering chromatin structure and can account for the apparent conservation of SWI and SNF proteins in eukaryotes other than yeast.
许多酵母基因的转录需要SWI/SNF调节复合物。先前的研究表明，swi和snf突变体中HO基因转录的减少可被SIN1和SIN2基因的突变部分缓解。我们在此表明，SIN2与编码组蛋白H3的两个基因之一HHT1相同，并且任一基因的突变都可导致Sin-表型。这些突变对野生型具有部分显性，并导致组蛋白H3结构域中三个保守位置的氨基酸替换。我们还鉴定出了影响组蛋白H4的组蛋白折叠结构域中两个保守位置的部分显性sin突变。三个sin突变影响与DNA相互作用的表面残基，并可能降低DNA与组蛋白八聚体的亲和力。两个sin突变影响组蛋白八聚体的（H2A-H2B）二聚体和（H3-H4）2四聚体亚基之间界面处或附近的残基，并可能影响核小体的稳定性或构象。影响组蛋白八聚体结构的突变能够缓解对SWI和SNF产物的需求，这支持了SWI/SNF复合物通过改变染色质结构来刺激转录的观点，并且可以解释酵母以外的真核生物中SWI和SNF蛋白明显保守的原因。
