Chromosomal clustering of genes controlled by the aire transcription factor
Chromosomal clustering of genes controlled by the aire transcription factor
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DOI：
10.1073/pnas.0502670102
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发表时间：
2005-05-17
影响因子：
11.1
通讯作者：
Mathis, DJ
中科院分区：
文献类型：
--
作者：
Johnnidis, JB;Venanzi, ES;Mathis, DJ
自身免疫调节因子（aire）是一种控制T细胞库自身反应性的转录因子。尽管先前的结果表明，它部分地通过促进胸腺髓上皮细胞中一系列外周组织抗原的异位表达来发挥这种功能，但最近的数据表明，它在髓细胞对胸腺细胞的阴性选择中起着额外的作用。作为探索这种作用的一种方法，我们对空气缺乏小鼠与野生型小鼠的髓质RNA转录物的微阵列数据进行了计算分析，重点关注空气控制基因的基因组定位。我们的研究结果。强调该分子的转录激活和沉默作用，并揭示其靶基因的显著聚类程度。在局部范围内，空气调节的基因簇呈点状，空气控制和空气独立的基因常常被穿插在一起。这种模式表明，aire的作用可能不是染色质重塑酶广泛作用的简单反映。对某些聚集基因的身份分析，使人联想到空气在抗原呈递和胸腺内细胞迁移协调中的潜在作用：例如，主要组织相容性复合体I类和II类基因产物和某些趋化因子基因是空气调节转录的靶标。
Autoimmune regulator (aire) is a transcription factor that controls the self-reactivity of the T cell repertoire. Although previous results indicate that it exerts this function in part by promoting ectopic expression of a battery of peripheral-tissue antigens in epithelial cells of the thymic medulla, recent data argue for additional roles in negative selection of thymocytes by medullary cells. As one approach to exploring such roles, we performed computational analyses of microarray data on medullary RNA transcripts from aire-deficient versus wild-type mice, focusing on the genomic localization of aire-controlled genes. Our results. highlight this molecule's transcriptional activating and silencing roles and reveal a significant degree of clustering of its target genes. On a local scale, aire-regulated clusters appeared punctate, with aire-controlled and aire-independent genes often being interspersed. This pattern suggests that aire's action may not be a simple reflection of the wide action of a chromatin remodeling enzyme. Analysis of the identity of certain of the clustered genes was evocative of aire's potential roles in antigen presentation and the coordination of intrathymic cell migration: for example, major histocompatibility complex class I and class II gene products and certain chemokine genes are targets of aire-regulated transcription.