GLOBAL ALTERATIONS IN CHROMATIN ACCESSIBILITY ASSOCIATED WITH LOSS OFSIN4 FUNCTION

Sin4p is a component of a mediator complex associated with the C-termi nal domain of RNA polymerase ii and SIN4 is required for proper regula tion of several genes in yeast, including the HO endonuclease gene, gl ucose repressible genes and MATa cell-specific genes. Previous studies indicated that SIN4 may influence transcription through changes in th e organization of chromatin, We have examined a specific chromatin str ucture associated with MAT alpha cell-specific repression in sin4 MATa cells to determine id SIN4 is required for nucleosome positioning, Al though the loss of SIN4 has no effect on nucleosome location, we find that the sensitivity of bulk chromatin from sin4 cells to micrococcal nuclease digestion is strikingly increased relative to chromatin from isogenic wild-type cells, The nuclease hypersensitivity of chromatin f rom sin4 cells is not related to gross alterations in histone gene exp ression or to bulk Increases in histone modification, Our experiments suggest that SIN4 directly or indirectly regulates a global aspect of chromatin accessibility, providing a molecular basis for phenotypic si milarities between sin4 mutations and mutations in histones.