RESUMO
The protein lysine methyltransferase SET domain-containing protein 6 (SETD6) has been shown to influence different cellular activities and to be critically involved in the regulation of diverse developmental and pathological processes. However, the upstream signals that regulate the mRNA expression of SETD6 are not known. Bioinformatic analysis revealed that the SETD6 promoter has a binding site for the transcription factor E2F1. Using various experimental approaches, we show that E2F1 binds to the SETD6 promoter and regulates SETD6 mRNA expression. Our further observation that this phenomenon is SETD6 dependent suggested that SETD6 and E2F1 are linked. We next demonstrate that SETD6 monomethylates E2F1 specifically at K117 in vitro and in cells. Finally, we show that E2F1 methylation at K117 positively regulates the expression level of SETD6 mRNA. Depletion of SETD6 or overexpression of E2F1 K117R mutant, which cannot be methylated by SETD6, reverses the effect. Taken together, our data provide evidence for a positive feedback mechanism, which regulates the expression of SETD6 by E2F1 in a SETD6 methylation-dependent manner, and highlight the importance of protein lysine methyltransferases and lysine methylation signaling in the regulation of gene transcription.
RESUMO
BACKGROUND: Both caudal epidural and ilioinguinal/iliohypogastric nerve blocks have been used to provide effective intra- and postoperative analgesia. Stress response hormone levels can be used as an objective method to assess the analgesic efficacy of the anaesthetic techniques used in infraumbilical surgery in children. In this study, we compared catecholamine blood levels in children undergoing these two different supplementary analgesic/anaesthetic techniques. METHODS: Thirty male paediatric patients undergoing orchidopexy, ASA I, received inhalation general anaesthesia, and were randomly allocated to one of two groups: a caudal group (n = 15) and an ilioinguinal/iliohypogastric nerve block group (n = 15). Plasma epinephrine and norepinephrine concentrations were measured at the induction time, at the end of surgery, and in the postanaesthesia care unit. Postoperative pain score was also assessed in the postanaesthesia care unit. RESULTS: In both groups, there was a substantial decrease in the catecholamine blood levels; however, there were significantly higher levels of epinephrine in the ilioinguinal group at the end of surgery (P = 0.008) and in the recovery room (P = 0.02) and a significant higher level of norpinephrine in the recovery room (P = 0.008). CONCLUSIONS: The result of this study revealed that caudal epidural block was more effective than ilioinguinal block in suppressing the stress response as reflected in epinephrine and norepinephrine blood levels in orchidopexy patients.
