The CD8α gene locus is regulated by the Ikaros family of proteins
The CD8α gene locus is regulated by the Ikaros family of proteins
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DOI：
10.1016/s1097-2765(02)00711-6
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发表时间：
2002-12-01
期刊：
影响因子：
16
通讯作者：
Kioussis, D
中科院分区：
文献类型：
--
作者：
Harker, N;Naito, T;Kioussis, D
Ikaros家族成员是淋巴细胞发育的重要调节因子。在这里，我们表明，Ikaros可能在CD4与CD8谱系承诺决定中发挥重要作用，通过证明：（1）使用胸腺细胞染色质免疫沉淀，其在体内结合内源性CD8 α基因座中的调节元件，（2）Ikaros抑制由CD8调节元件驱动的转基因的位置效应杂色，和（3）Ikaros和Aiolos水平降低的小鼠显示具有不成熟表型的CD4群体明显增加，即，未能激活CD8 α基因位点的细胞。我们认为Ikaros家族成员的功能是CD8 α的激活剂。基因位点，以及它们的相关活性对于胸腺细胞分化和谱系定型过程中适当的染色质重塑转变至关重要。
Ikaros family members are important regulatory factors in lymphocyte development. Here we show that Ikaros may play an important role in CD4 versus CD8 lineage commitment decisions by demonstrating: (1) that it binds to regulatory elements in the endogenous CD8alpha locus in vivo using thymocyte chromatin immunoprecipitations, (2) that Ikaros suppresses position effect variegation of transgenes driven by CD8 regulatory elements, and (3) that mice with reduced levels of Ikaros and Aiolos show an apparent increase in CD4 populations with immature phenotype, i.e., cells that failed to activate the CD8alpha gene locus. We propose that Ikaros family members function as activators of the CD8alpha. gene locus and that their associated activities are critical for appropriate chromatin remodeling transitions during thymocyte differentiation and lineage commitment.