Molecular characterization and mapping of ATOH7, a human atonal homolog with a predicted role in retinal ganglion cell development
Molecular characterization and mapping of ATOH7, a human atonal homolog with a predicted role in retinal ganglion cell development
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DOI：
10.1007/s00335-001-2101-3
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发表时间：
2002-02-01
期刊：
影响因子：
2.5
通讯作者：
Glaser, T
中科院分区：
文献类型：
--
作者：
Brown, NL;Dagenais, SL;Glaser, T
人类ATOH7基因编码一个碱性螺旋-环-螺旋(BHLH)转录因子，该转录因子与果蝇高度相似，在保守的bHLH结构域内。ATOH7编码区包含在单个外显子内。我们将ATOH7定位于染色体(Chr)10q21.3-22.1，这是一个与小鼠Chr 10片段同线的区域，Atoh7(以前称为Maths)所在的片段。用简约分析研究了ATOH7与其他无性同系物的进化关系。ATH5/7和ATH1蛋白亚组与无机酸的直接比较也揭示了氨基酸变化在bHLH域的非随机分布，这可能与它们各自独立的视觉和本体感觉功能有关。在bHLH基因中，ATOH7与Atoh7关系最为密切。这种序列保守性大大超出了编码区。我们在人类和小鼠基因组DNA两侧定义了强同源性的块，其中可能包括顺式调控元件。由于AtoH7的靶向缺失会导致小鼠视神经发育不全，我们建议将ATOH7作为人类视神经发育不全和相关临床症状的候选基因。
The human ATOH7 gene encodes a basic helix-loop-helix (bHLH) transcription factor that is highly similar to Drosophila Atonal within the conserved bHLH domain. The ATOH7 coding region is contained within a single exon. We mapped ATOH7 to Chromosome (Chr) 10q21.3-22.1, a region syntenic to the segment of mouse Chr 10 where Atoh7 (formerly Maths) is located. The evolutionary relationship between ATOH7 and other atonal homologs was investigated using parsimony analysis. A direct comparison of ATH5/7 and ATH1 protein subgroups to Atonal also revealed a nonrandom distribution of amino acid changes across the bHLH domain, which may be related to their separate visual and proprioceptive sensory functions. Among bHLH genes, ATOH7 is most closely related to Atoh7. This sequence conservation extends significantly beyond the coding region. We define blocks of strong homology in flanking human and mouse genomic DNA, which are likely to include cis regulatory elements. Because targeted deletion of Atoh7 causes optic nerve agenesis in mice, we propose ATOH7 as a candidate for human optic nerve aplasia and related clinical syndromes.