Conserved co-regulation and promoter sharing of hoxb3a and hoxb4a in zebrafish
Conserved co-regulation and promoter sharing of hoxb3a and hoxb4a in zebrafish
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DOI：
10.1016/j.ydbio.2006.04.446
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发表时间：
2006-09-01
影响因子：
2.7
通讯作者：
Rinkwitz, Silke
中科院分区：
文献类型：
--
作者：
Hadrys, Thorsten;Punnamoottil, Beena;Rinkwitz, Silke
斑马鱼hoxb 3a和hoxb 4a的表达被发现通过五个转录本介导，hoxb 3a转录本I-III和hoxb 4a转录本I-II，由四个启动子驱动。位于hoxb 5a下游约2kb的“主”启动子控制包含两个基因的外显子序列的前mRNA的转录。这种独特的基因结构提出了一种新的机制，以确保重叠，组织特异性表达的两个基因在后后脑和脊髓。转基因方法被用来分析斑马鱼hoxb 3a/hoxb 4a的启动子和增强子序列的功能，包含以前通过比较基因组学确定的同源区域。两个神经增强子被证明在后脑内建立特定的前表达边界，并介导来自后脑菱球（r）5至8的定义的神经元群体中的表达，这表明基因在神经元细胞谱系特化中的晚期作用。物种比较显示，斑马鱼hoxb 3a r5和r6增强子对应于小鼠HoxA簇内的序列，该序列控制Hoxa 3在r5和r6中的活性，而HoxB簇内的同源区域激活Hoxb 3表达，但仅限于r5。我们的结论是hoxb 3a/Hoxa 3调控机制的相似性反映了这两个基因从一个单一的祖先paradox组3基因的共同血统。(c)2006爱思唯尔公司All rights reserved.
The expression of zebrafish hoxb3a and hoxb4a has been found to be mediated through five transcripts, hoxb3a transcripts I-III and hoxb4a transcripts I-II, driven by four promoters. A 'master' promoter, located about 2 kb downstream of hoxb5a, controls transcription of a pre-mRNA comprising exon sequences of both genes. This unique gene structure is proposed to provide a novel mechanism to ensure overlapping, tissue-specific expression of both genes in the posterior hindbrain and spinal cord. Transgenic approaches were used to analyze the functions of zebrafish hoxb3a/hoxb4a promoters and enhancer sequences containing regions of homology that were previously identified by comparative genomics. Two neural enhancers were shown to establish specific anterior expression borders within the hindbrain and mediate expression in defined neuronal populations derived from hindbrain rhombomeres (r) 5 to 8, suggesting a late role of the genes in neuronal cell lineage specification. Species comparison showed that the zebrafish hoxb3a r5 and r6 enhancer corresponded to a sequence within the mouse HoxA cluster controlling activity of Hoxa3 in r5 and r6, whereas a homologous region within the HoxB cluster activated Hoxb3 expression but limited to r5. We conclude that the similarity of hoxb3a/Hoxa3 regulatory mechanisms reflect the shared descent of both genes from a single ancestral paralog group 3 gene. (c) 2006 Elsevier Inc. All rights reserved.