Ripperger Jürgen A, Schibler Ueli
Department of Molecular Biology and National Center of Competence in Research Frontiers in Genetics, Sciences III, University of Geneva, 30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
Nat Genet. 2006 Mar;38(3):369-74. doi: 10.1038/ng1738. Epub 2006 Feb 12.
Mammalian circadian rhythms are based on transcriptional and post-translational feedback loops. Essentially, the activity of the transcription factors BMAL1 (also known as MOP3) and CLOCK is rhythmically counterbalanced by Period (PER) and Cryptochrome (CRY) proteins to govern time of day-dependent gene expression. Here we show that circadian regulation of the mouse albumin D element-binding protein (Dbp) gene involves rhythmic binding of BMAL1 and CLOCK and marked daily chromatin transitions. Thus, the Dbp transcription cycle is paralleled by binding of BMAL1 and CLOCK to multiple extra- and intragenic E boxes, acetylation of Lys9 of histone H3, trimethylation of Lys4 of histone H3 and a reduction of histone density. In contrast, the antiphasic daily repression cycle is accompanied by dimethylation of Lys9 of histone H3, the binding of heterochromatin protein 1alpha and an increase in histone density. The rhythmic conversion of transcriptionally permissive chromatin to facultative heterochromatin relies on the presence of functional BMAL1-CLOCK binding sites.
哺乳动物的昼夜节律基于转录和翻译后反馈环。本质上，转录因子BMAL1（也称为MOP3）和CLOCK的活性通过周期蛋白（PER）和隐花色素（CRY）蛋白进行节律性平衡，以控制昼夜依赖性基因表达的时间。我们在此表明，小鼠白蛋白D元件结合蛋白（Dbp）基因的昼夜调节涉及BMAL1和CLOCK的节律性结合以及显著的每日染色质转变。因此，Dbp转录周期与BMAL1和CLOCK与多个基因外和基因内E盒的结合、组蛋白H3赖氨酸9的乙酰化、组蛋白H3赖氨酸4的三甲基化以及组蛋白密度的降低并行。相反，反相的每日抑制周期伴随着组蛋白H3赖氨酸9的二甲基化、异染色质蛋白1α的结合以及组蛋白密度的增加。转录允许染色质向兼性异染色质的节律性转变依赖于功能性BMAL1 - CLOCK结合位点的存在。
