Combinatorial effects of splice variants modulate function of Aiolos
Combinatorial effects of splice variants modulate function of Aiolos
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DOI：
10.1242/jcs.007344
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发表时间：
2007-08-01
影响因子：
4
通讯作者：
Ballestar, Esteban
中科院分区：
文献类型：
--
作者：
Caballero, Rosalia;Setien, Fernando;Ballestar, Esteban
转录因子Aiolos(又称IKZF3)是锌指蛋白Ikaros家族的一员，在控制B淋巴细胞的分化和增殖中起着重要的作用。以前，已经描述了由差异剪接产生的Ikaros家族成员的多种异构体，现在我们报告了一些新的Aiolos异构体。已有研究表明，Ikaros家族的全长异构体定位于异染色质，并可与含组蛋白脱乙酰酶(HDAC)的复合体结合。在这项研究中，我们首次直接研究了不同的Aiolos亚型的细胞定位，它们与Ikaros异二聚化和与含有HDAC的复合体结合的能力，以及对组蛋白修饰和与可能的靶点结合的影响。我们的工作表明，Aiolos异构体的细胞活性依赖于不同功能结构域的组合，这些功能结构域是由mRNA转录本的差异剪接产生的。这些数据支持单个蛋白质的功能是通过选择性剪接来调节的一般原理，并突出了Aiolos在正常和异常淋巴细胞功能中的一些潜在影响。
The transcription factor Aiolos ( also known as IKZF3), a member of the Ikaros family of zinc-finger proteins, plays an important role in the control of B lymphocyte differentiation and proliferation. Previously, multiple isoforms of Ikaros family members arising from differential splicing have been described and we now report a number of novel isoforms of Aiolos. It has been demonstrated that full-length Ikaros family isoforms localize to heterochromatin and that they can associate with complexes containing histone deacetylase ( HDAC). In this study, for the first time we directly investigate the cellular localization of various Aiolos isoforms, their ability to heterodimerize with Ikaros and associate with HDAC-containing complexes, and the effects on histone modification and binding to putative targets. Our work demonstrates that the cellular activities of Aiolos isoforms are dependent on combinations of various functional domains arising from the differential splicing of mRNA transcripts. These data support the general principle that the function of an individual protein is modulated through alternative splicing, and highlight a number of potential implications for Aiolos in normal and aberrant lymphocyte function.