Promoter, alternative splice forms, and genomic structure of protocadherin 15
Promoter, alternative splice forms, and genomic structure of protocadherin 15
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DOI：
10.1016/j.ygeno.2007.06.007
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发表时间：
2007-10-01
期刊：
影响因子：
4.4
通讯作者：
Smith, Richard J.
中科院分区：
文献类型：
--
作者：
Alagramam, Kumar N.;Miller, Nathaniel D.;Smith, Richard J.
我们最初表明原钙粘蛋白15基因（Pcdh15）是听力和平衡功能所必需的；Pcdh15突变影响Ames waltzer（av）小鼠毛细胞发育。在这里，我们扩展了这项研究，以更好地了解Pcdh15如何在细胞中起作用。最初的报道在Pcdh15中发现了33个外显子，其中外显子1是非编码的；后来又报道了Pcdh15的其他外显子。最初描述的Pcdh15的33个外显子嵌入在409 kb的小鼠基因组序列中，而人类Pcdh15的相应外显子分布在980 kb的基因组DNA中；Pcdh15/ Pcdh15的外显子大小在9 ~ 2000 bp之间。Pcdh15/ Pcdh15的基因组组织与cadherin 23相似，但与其他原cadherin基因（如Pcdh α、β或γ）存在显著差异。CpG岛位于PCDH15转录起始位点上游2900 bp处。Pcdh15/ Pcdh15启动子在转录起始位点上游100个碱基内缺乏TATAA或CAAT序列；缺失图谱显示Pcdh15含有抑制元件和增强元件。对Pcdh15的选择性剪接转录本的初步搜索发现了以前未报道的新的剪接变体。我们的研究结果表明，小鼠和人类原钙粘蛋白15基因都具有复杂的基因组结构和转录控制机制。(C) 2007爱思唯尔公司版权所有。
We originally showed that the protocadherin 15 gene (Pcdh15) is necessary for hearing and balance functions; mutations in Pcdh15 affect hair cell development in Ames waltzer(av) mice. Here we extend that study to understand better how Pcdh15 operates in a cell. The original report identified 33 exons in Pcdh15, with exon 1 being noncoding; additional exons of Pcdh15 have since been reported. The 33 exons of Pcdh15 described originally are embedded in 409 kb of mouse genomic sequence, while the corresponding exons of human PCDH15 are spread over 980 kb of genomic DNA; the exons in Pcdh15/PCDH15 range in size from 9 to similar to 2000 bp. The genomic organization of Pcdh15/PCDH15 bears similarity to that of cadherin 23, but differs significantly from other protocadherin genes, such as Pcdh alpha, beta or gamma. A CpG island is located similar to 2900 bp upstream of the PCDH15 transcriptional start site. The Pcdh15/PCDH15 promoter lacks TATAA or CAAT sequences within 100 bases upstream of the transcription start site; deletion mapping showed that Pcdh15 harbors suppressor and enhancer elements. Preliminary searches for alternatively spliced transcripts of Pcdh15 identified novel splice variants not reported previously. Results from our study show that both mouse and human protocadherin 15 genes have complex genomic structures and transcription control mechanisms. (C) 2007 Elsevier Inc. All rights reserved.