RPD3 disruption represses genes near telomeric ends.
(A) RPD3 deletion and histone H4
depletion both regulate genes within 15–20 kb of telomere ends. In
contrast, SIR2 deletion regulates genes within 5–10 kb of these ends
(13). (B) Like RPD3 deletion, TSA
treatment down-regulates telomeric genes. Telomeric genes sensitive to
SIR deletion (12) are repressed rapidly by TSA. Telomeric genes
sensitive to H4 depletion (13) are slowly repressed by TSA. Like
RPD3 deletion, TSA up-regulates histone genes. Taken
together, these data support a model in which RPD3
abrogates telomeric silencing via the direct and indirect mechanisms
outlined in C. (C) Rpd3p appears to
activate telomeric genes directly by deacetylating histone H4 lysine 12
and, thereby, hindering repression by SIR proteins. Rpd3p appears to
activate telomeric genes indirectly by repressing histone genes.