Gaudry Michael J, Campbell Kevin L
Department of Biological Sciences, University of ManitobaWinnipeg, MB, Canada.
Front Physiol. 2017 Sep 20;8:670. doi: 10.3389/fphys.2017.00670. eCollection 2017.
Uncoupling protein 1 (UCP1) permits non-shivering thermogenesis (NST) when highly expressed in brown adipose tissue (BAT) mitochondria. Exclusive to placental mammals, BAT has commonly been regarded to be advantageous for thermoregulation in hibernators, small-bodied species, and the neonates of larger species. While numerous regulatory control motifs associated with transcription have been proposed for murid rodents, it remains unclear whether these are conserved across the eutherian mammal phylogeny and hence essential for UCP1 expression. To address this shortcoming, we conducted a broad comparative survey of putative transcriptional regulatory elements in 139 mammals (135 eutherians). We find no evidence for presence of a enhancer in monotremes and marsupials, supporting the hypothesis that this control region evolved in a stem eutherian ancestor. We additionally reveal that several putative promoter elements (e.g., CRE-4, CCAAT) identified in murid rodents are not conserved among BAT-expressing eutherians, and together with the putative regulatory region (PRR) and CpG island do not appear to be crucial for UCP1 expression. The specificity and importance of the upTRE, dnTRE, URE1, CRE-2, RARE-2, NBRE, BRE-1, and BRE-2 enhancer elements first described from rats and mice are moreover uncertain as these motifs differ substantially-but generally remain highly conserved-in other BAT-expressing eutherians. Other enhancer motifs (CRE-3, PPRE, and RARE-3) as well as the TATA box are also highly conserved in nearly all eutherian lineages with an intact . While these transcriptional regulatory motifs are generally also maintained in species where this gene is pseudogenized, the loss or degeneration of key basal promoter (e.g., TATA box) and enhancer elements in other -lacking lineages make it unlikely that the enhancer region is pleiotropic (i.e., co-regulates additional genes). Importantly, differential losses of (or mutations within) putative regulatory elements among the eutherian lineages with an intact suggests that the transcriptional control of gene expression is not highly conserved in this mammalian clade.
解偶联蛋白1（UCP1）在棕色脂肪组织（BAT）线粒体中高度表达时可实现非颤抖性产热（NST）。BAT为胎盘哺乳动物所特有，通常被认为对冬眠动物、小型物种以及大型物种的新生儿的体温调节具有优势。虽然已针对家鼠提出了许多与转录相关的调控控制基序，但尚不清楚这些基序在真兽类哺乳动物系统发育中是否保守，因此对于UCP1表达是否必不可少。为解决这一缺陷，我们对139种哺乳动物（135种真兽类）中的假定转录调控元件进行了广泛的比较研究。我们没有发现单孔目动物和有袋目动物中存在增强子的证据，这支持了该调控区域在真兽类祖先中进化的假说。我们还发现，在家鼠中鉴定出的几个假定启动子元件（如CRE-4、CCAAT）在表达BAT的真兽类中并不保守，并且与假定调控区域（PRR）和CpG岛一起似乎对UCP1表达并不关键。此外，最初在大鼠和小鼠中描述的upTRE、dnTRE、URE1、CRE-2、RARE-2、NBRE、BRE-1和BRE-2增强子元件的特异性和重要性尚不确定，因为这些基序在其他表达BAT的真兽类中有很大差异，但通常仍高度保守。其他增强子基序（CRE-3、PPRE和RARE-3）以及TATA框在几乎所有具有完整[此处原文缺失相关内容]的真兽类谱系中也高度保守。虽然这些转录调控基序在该基因假基因化的物种中通常也得以保留，但在其他缺乏[此处原文缺失相关内容]的谱系中关键基础启动子（如TATA框）和增强子元件的缺失或退化使得增强子区域不太可能具有多效性（即共同调控其他基因）。重要的是，在具有完整[此处原文缺失相关内容]的真兽类谱系中，假定调控元件的差异丢失（或突变）表明该哺乳动物类群中基因表达的转录调控并非高度保守。
