法洛四联症患儿组蛋白乙酰化及其酶的表达  

Histone acetylation and expression of acetylation-related enzymes in children with tetralogy of Fallot

作　　者：徐君[1,2] 林怡翔[1,2] 顾若漪[1,2] 王慧君[1,2] 马晓静[1,2] 马端 黄国英[1,2] 

机构地区：[1]复旦大学附属儿科医院,上海201102 [2]上海市出生缺陷防治重点实验室,上海200032

出　　处：《中国当代儿科杂志》2013年第10期817-821,共5页Chinese Journal of Contemporary Pediatrics

基　　金：国家"973"项目(2010CB529504);国家自然科学基金重点项目(30930096);上海市科委员科研计划连续资助项目(11JC1401400)

摘　　要：目的观察组蛋白乙酰转移酶(HATs)及组蛋白去乙酰化酶(HDACs)在法洛四联症(TOF)患儿中的表达情况,探讨组蛋白乙酰化及其酶在TOF发病中的作用。方法 TOF组心肌组织标本来源于46例行TOF根治术患儿,对照组心肌组织标本来源于16例意外死亡经尸检未发现心脏畸形的儿童。采用免疫组织化学染色法检测TOF组和对照组中H3K9、H3K18、H3K27 3个组蛋白乙酰化位点的乙酰化水平;采用Realtime PCR技术筛选TOF组与对照组心肌组织中组蛋白乙酰化相关酶HATs和HDACs的mRNA表达水平,并分析其与组蛋白乙酰化水平的相关性。结果与对照组比较,TOF组H3K9位点的乙酰化水平明显增高(P=0.0165);而H3K18、H3K27两个位点的乙酰化水平明显降低(均P<0.05)。分别对4个HATs和6个HDACs检测发现,TOF组中EP300和CBP mRNA水平较对照组升高(均P<0.05);而其他HATs和HDACs mRNA表达水平在两组间差异均无统计学意义(均P>0.05)。相关分析显示,H3K9乙酰化水平与EP300和CBP mRNA表达呈显著正相关(分别r=0.71、0.72,均P<0.01)。结论 H3K9乙酰化水平增高可能与EP300和CBP mRNA表达上调呈正相关,提示EP300和CBP可能是通过调控H3K9乙酰化状态影响心脏发育。Objective To study the expression of histone acetyltransferases （HATs） and histone deacetylases （HDACs） in children with tetralogy of Fallot （TOF）, and to investigate the role of histone acetylation and acetylation- related enzymes in the pathogenesis of TOE Methods Myocardial tissue samples in the TOF group were obtained from 46 children with TOF who underwent radical operation, and myocardial tissue samples in the control group were obtained from 16 children who suffered accidental deaths and had no cardiac anomalies as shown by autopsy. The acetylation of H3K9, H3K18 and H3K27 was evaluated by immunohistochemistry. The mRNA expression of HATs and HDACs in the myocardium was measured by real-time PCR. The correlation between mRNA expression of HATs and HDACs and histone acetylation was analyzed. Results Compared with the control group, the TOF group showed significantly increased acetylation of H3K9 （P=0.0165） and significantly decreased acetylation of H3K18 （P=0.0048） and H3K27 （P=-0.0084）. As to 4 HATs and 6 HDACs, the mRNA expression of EP300 and CBP was significantly higher in the TOF group than in the control group （P=0.025; P=0.017）, and there was no significant difference in the mRNA expression of other HATs and HDACs between the two groups. The correlation analysis revealed a positive correlation between H3K9 acetylation and mRNA expression of EP300 （r=0.71, P〈0.01） and CBP （r=0.72, P〈0.01）. Conclusions Upregulated mRNA expression of EP300 and CBP may be associated with increased H3K9 acetylation, suggesting that EP300 and CBP might affect cardiac development by regulating H3K9 acetylation.

关 键 词：组蛋白乙酰化 组蛋白乙酰转移酶 组蛋白去乙酰化酶 法洛四联症 儿童 

分 类 号：R725.4[医药卫生—儿科]