Low-temperature radiofrequency applications that cause transient AP block predict permanent success when a higher-temperature application is delivered at the same site. The time to achieve conduction block is a function of the temperature set point, and low-temperature tests produce reversible conduction block, suggesting minimal permanent injury.
Acetylation of histones plays a critical role in maintaining the epigenetic state of the eukaryotic cell. One such acetylation site critical for DNA damage repair is H3K56ac. In Saccharomyces cerevisiae, H3K56ac is thought to be driven mainly by Rtt109, a lysine acetyltransferase (KAT) that associates with the histone chaperones Vps75 and Asf1. Both of these chaperones can increase the specificity of histone acetylation by Rtt109, but neither alter the selectivity. It has been shown that histones extracted from cells (Drosophila), presumably containing pre-acetylated histones, can incorporate higher amounts of H3K56ac relative to recombinant non-acetylated histones. We hypothesized that histone pre-acetylation and histone chaperones could function together to drive acetylation of H3K56. In the present study, we test this hypothesis using a series of singly acetylated histones to determine the impact of crosstalk on enzyme selectivity. Our data suggest that crosstalk between acetylation sites plays a major role in altering the selectivity of Rtt109-Vps75 and that the histone chaperone Asf1 mediates this crosstalk. Specifically, we show that H3K14ac/H4 functions with Asf1 to drive H3K56ac by Rtt109-Vps75. We identified an acidic patch in Asf1 that mediates this cross-talk and show that mutations to this region can alter the Asf1 mediated crosstalk that changes Rtt109-Vps75 selectivity. These data explain the genetic link between Gcn5, which acetylates H3K14 and Rtt109.
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