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.