Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland - involvement of cAMP-responsive element modulator in epigenetic regulation of Cyp17a1
Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland - involvement of cAMP-responsive element modulator in epigenetic regulation of Cyp17a1
复制标题
DOI：
10.1111/j.1742-4658.2011.08317.x
复制
发表时间：
2012-05-01
期刊：
影响因子：
5.4
通讯作者：
Rozman, Damjana
中科院分区：
文献类型：
--
作者：
Kosir, Rok;Zmrzljak, Ursula Prosenc;Rozman, Damjana
细胞色素P450（CYP）基因Cyp51、Cyp11a1、Cyp17a1、Cyp11b1、Cyp11b2和Cyp21a1参与肾上腺皮质类固醇的产生，其循环水平是昼夜节律的。cAMP信号在肾上腺类固醇生成中起重要作用。通过使用cAMP反应元件调节剂（Crem）敲除小鼠，我们表明CREM亚型有助于小鼠肾上腺中类固醇生成CYP的昼夜表达。最引人注目的是CREM依赖性的低甲基化Cyp17a1启动子在zeitgeber时间12，这导致更高的Cyp17a1 mRNA和蛋白质表达在敲除肾上腺。这些数据表明Crem基因的产物控制Cyp17在小鼠肾上腺中的表观遗传抑制。
The cytochrome P450 (CYP) genes Cyp51, Cyp11a1, Cyp17a1, Cyb11b1, Cyp11b2 and Cyp21a1 are involved in the adrenal production of corticosteroids, whose circulating levels are circadian. cAMP signaling plays an important role in adrenal steroidogenesis. By using cAMP responsive element modulator (Crem) knockout mice, we show that CREM isoforms contribute to circadian expression of steroidogenic CYPs in the mouse adrenal gland. Most striking was the CREM-dependent hypomethylation of the Cyp17a1 promoter at zeitgeber time 12, which resulted in higher Cyp17a1 mRNA and protein expression in the knockout adrenal glands. The data indicate that products of the Crem gene control the epigenetic repression of Cyp17 in mouse adrenal glands.