Pituitary homeodomain transcription factors HESX1 and PROP1 form a heterodimer on the inverted TAAT motif
Pituitary homeodomain transcription factors HESX1 and PROP1 form a heterodimer on the inverted TAAT motif
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DOI：
10.1016/j.mce.2009.10.006
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发表时间：
2010-02-05
影响因子：
4.1
通讯作者：
Kato, Takako
中科院分区：
文献类型：
--
作者：
Kato, Yukio;Kimoto, Fuyuko;Kato, Takako
垂体的发育和分化过程中，许多转录因子的时空表达。转录因子HESX 1在垂体发育的早期阶段开始在Rathke囊中表达，充当转录阻遏物。另一种转录因子PROM是一种垂体特异性因子，对决定垂体腺瘤细胞的分化很重要，其出现晚于HESX 1，并被认为阻断HESX 1的作用。这两种因子都是同源结构域家族的成员，同源结构域第50位的氨基酸残基是谷氨酰胺（Gln-50）。我们最近观察到，这两种因子通过不同的结合谱共享相同的靶序列。因此，使用随机寡核苷酸和电泳迁移率变动分析，我们已经检查了DNA结合的HESX 1的优先权，通过确定其结合序列。HESX 1作为单体与TAATT基序结合，但不与TAAT基序结合。在PROP 1的存在下，HESX 1通过形成异二聚体与反向TAAT基序结合。因此，HESX 1和PROP 1之间的异二聚体的形成提供了一种条件，其中在早期垂体原基中，HESX 1通过与新出现的PROP 1形成异二聚体而将其抑制作用改变为活性作用，使得PROP 1最终取代HESX 1以推进到垂体发育的中期。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
The development and differentiation of the pituitary gland progress through spatial and temporal expressions of many transcription factors. Transcription factor HESX1, which begins to be expressed in the Rathke's pouch at the early stage of pituitary development, acts as a transcription repressor. Another transcription factor, PROM, which is a pituitary-specific factor and important for the determination of the differentiation of pituitary hormone-producing cells, appears later than HESX1 and is assumed to block the action of HESX1. Both factors are members of the homeodomain family, and the amino acid residue at the 50th position of the homeodomain is glutamine (Gln-50). We recently observed that both factors share the same target sequence through different binding profiles. Hence, using random oligonucleotides and an electrophoretic mobility-shift assay, we have examined the DNA-binding preference of HESX1 by a determination of its binding sequence. HESX1 binds as a monomer to a TAATT motif but not to a TAAT motif. In the presence of PROP1, HESX1 develops to bind to an inverted TAAT motif by forming a heterodimer. Thus, the formation of a heterodimer between HESX1 and PROP1 provides a condition in which, in the early pituitary primordium, HESX1 alters its repressive role to an active one by forming a heterodimer with newly appearing PROP1 so that PROP1 finally replaces HESX1 to advance to the middle stage of pituitary development. (C) 2009 Elsevier Ireland Ltd. All rights reserved.