Stable nucleosome positioning and complete repression by the yeast alpha 2 repressor are disrupted by amino-terminal mutations in histone H4.

Nucleosomes are positioned in the presence of the yeast repressor alpha 2 in minichromosomes containing the alpha 2 operator and on the promoters of a-cell-specific genes regulated by alpha 2. To investigate the possibility that alpha 2 directs nucleosome position through an interaction with a component of the core particle, we analyzed chromatin structures adjacent to the operator in alpha cells containing mutations in the amino-terminal region of histone H4. Deletion or point mutation of specific amino acids in histone H4 altered the location and/or stability of nucleosomes adjacent to the alpha 2 operator. These changes in chromatin structure were accompanied by partial derepression of a beta-galactosidase reporter construct under alpha 2 control, even though alpha 2 remained bound to its operator sequence. Our data suggest that complete repression by alpha 2 requires stable positioning of nucleosomes in promoter regions and this positioning involves the conserved amino-terminal region of histone H4.