Sequence and functional conservation of the intergenic region between the head-to-head genes encoding the small heat shock proteins αB-crystallin and HspB2 in the mammalian lineage
Sequence and functional conservation of the intergenic region between the head-to-head genes encoding the small heat shock proteins αB-crystallin and HspB2 in the mammalian lineage
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DOI：
10.1007/s00239-004-2659-y
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发表时间：
2004-11-01
影响因子：
3.9
通讯作者：
Lubsen, NH
中科院分区：
文献类型：
--
作者：
Doerwald, L;van Rheede, T;Lubsen, NH
大型哺乳动物基因组的一个意想不到的特征是经常出现紧密连锁的头对头基因对。这种基因对的紧密并列被认为是由于调控元件的共享。我们在这里表明，头对头基因对编码两个小的热休克蛋白，α B-晶体蛋白和HspB 2，是紧密相连的所有主要的哺乳动物分支，这表明这种紧密的联系是选择性的优势。然而，α B-晶状体蛋白在透镜和肌肉中大量表达，并且响应于热休克，而HspB 2仅在肌肉中大量表达，并且不被热休克上调。在哺乳动物中，这两种蛋白质的基因间距离范围从645 bp（鸭嘴兽）到1069 bp（负鼠），平均约为900 bp;在鸡中，距离与鸭相同（1.6 kb）。系统发育足迹和序列比对确定了一些保守的序列元件接近HspB 2启动子和两个更远的上游。除了鸭嘴兽和鸟类外，所有已知的小鼠α B-晶状体蛋白启动子调控元件都是保守的。在鸟类中缺少晶状体特异性区域1（LSR 1）和热休克元件（HSEs）;在鸭嘴兽中，LSR 1减少到Pax-6位点，而LSR 2中的Pax-6位点和HSE缺失。最可能的是原始哺乳动物α B-晶状体蛋白启动子具有两个LSR和两个HSE。在转染实验中，鸭嘴兽α B-晶状体蛋白启动子保留热休克反应性和透镜表达。它还指导非洲爪蟾转基因中的透镜表达，就像大鼠或盲鼹鼠的HspB 2启动子一样。删除中间的基因间区域，包括上游增强子的影响的活性的大鼠α B-晶状体蛋白和HspB 2启动子，这表明共享的增强子区域的两个启动子。
An unexpected feature of the large mammalian genome is the frequent occurrence of closely linked head-to-head gene pairs. Close apposition of such gene pairs has been suggested to be due to sharing of regulatory elements. We show here that the head-to-head gene pair encoding two small heat shock proteins, alphaB-crystallin and HspB2, is closely linked in all major mammalian clades, suggesting that this close linkage is of selective advantage. Yet alphaB-crystallin is abundantly expressed in lens and muscle and in response to a heat shock, while HspB2 is abundant only in muscle and not upregulated by a heat shock. The intergenic distance between the genes for these two proteins in mammals ranges from 645 bp (platypus) to 1069 bp (opossum), with an average of about 900 bp; in chicken the distance was the same as in duck (1.6 kb). Phylogenetic foot-printing and sequence alignment identified a number of conserved sequence elements close to the HspB2 promoter and two farther upstream. All known regulatory elements of the mouse alphaB-crystallin promoter are conserved, except in platypus and birds. The lens-specific region 1 (LSR1) and the heat shock elements (HSEs) lack in birds; in platypus the LSR1 is reduced to a Pax-6 site, while the Pax-6 site in LSR2 and a HSE are absent. Most likely the primordial mammalian alphaB-crystallin promoter had two LSRs and two HSEs. In transfection experiments the platypus alphaB-crystallin promoter retained heat shock responsiveness and lens expression. It also directed lens expression in Xenopus laevis transgenes, as did the HspB2 promoter of rat or blind mole rat. Deletion of the middle of the intergenic region including the upstream enhancer affected the activity of both the rat alphaB-crystallin and the HspB2 promoters, suggesting sharing of the enhancer region by the two promoters.