Molecular analysis of TBL1Y, a Y-linked homologue of TBL1X related with X-linked late-onset sensorineural deafness
Molecular analysis of TBL1Y, a Y-linked homologue of TBL1X related with X-linked late-onset sensorineural deafness
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DOI：
10.1007/s10038-005-0237-9
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发表时间：
2005-04-01
影响因子：
3.5
通讯作者：
Nakahori, Y
中科院分区：
文献类型：
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作者：
Yan, HT;Shinka, T;Nakahori, Y
人类Y染色体测序的最新进展揭示了一系列X-Y同源基因。在本研究中，我们重点研究了转导蛋白β样1Y (Transducin β -like 1Y, TBL1Y)，它是TBL1X的y连锁同源物，与x连锁的晚发性感音神经性耳聋有关。最近，研究表明，位于3号染色体上的另一个同源基因TBLR1和TBL1X作为几种核受体和转录因子的辅抑制因子/辅激活因子交换体。然而，TBL1Y的表达模式和功能尚不清楚。TBL1家族的RT-PCR分析显示，TBL1Y在所有13个检查组织中表达，但在白细胞中不表达。然而，在测试的细胞系中，它仅在NT2/D1细胞和EB病毒转化的淋巴母细胞中表达。为了比较TBL1家族的功能，我们生成了一系列TBL1家族gal4dbd融合蛋白的表达质粒。我们将这些质粒与含有5xGAL4结合位点的荧光素酶报告基因的质粒结合，进行了双荧光素酶测定。与其他构建体不同，融合gal4dbd的TBL1Y不抑制启动子活性。此外，我们在TBL1Y基因中发现了三个新的多态性，IVS7+9G > A， G268C和IVS7+1G > C，这些多态性被认为是导致剪接错误的原因。这些多态性在y -单倍群O3 （XO3e）中的男性中发现，这被定义为y -单倍群O3，不包括O3e， O3的一个分支。结果表明，TBL1Y在表达和功能上不同于TBL1家族的其他成员，提示其在男性中有其他作用。
Recent progress in sequencing the human Y chromosome has unveiled a series of X-Y homologous genes. In the present study, we focused on Transducin beta-like 1Y (TBL1Y), which is a Y-linked homologue of TBL1X that is related with X-linked late-onset sensorineural deafness. Recently, it has been shown that TBLR1, another homologue whose gene resides on chromosome 3, and TBL1X act as a corepressor/coactivator exchanger for several nuclear receptors and transcription factors. However, the expression pattern and function of TBL1Y remain unknown. The RT-PCR analysis of the TBL1 family revealed that TBL1Y was expressed in all 13 tissues examined but not in leukocytes. Among the cell lines tested, however, it was only expressed in NT2/D1 cells and in lymphoblasts transformed with Epstein Barr (EB) virus. To compare the functions of the TBL1 family, we generated a series of expression plasmids for GAL4DBD-fused proteins of the TBL1 family. We carried out dual luciferase assays using these plasmids in combination with a plasmid having a luciferase reporter gene harboring 5xGAL4 binding sites. Unlike the other constructs, GAL4DBD-fused TBL1Y did not repress the promoter activity. Moreover, we found three novel polymorphisms in the TBL1Y gene, IVS7+9G > A, G268C, and IVS7+1G > C, which is presumed to cause splicing error. These polymorphisms are found in males within Y-haplogroup O3 (XO3e), which is defined as the Y-haplogroup O3 excluding O3e, a branch of O3. The results show that TBL1Y differs from other members of the TBL1 family in expression and function, suggesting other roles in maleness.