Genetically separable determinants of hair keratin gene expression
Genetically separable determinants of hair keratin gene expression
复制标题
头发角蛋白基因表达的遗传可分离决定因素
DOI：
10.1002/1097-0177(200007)218:3
复制
发表时间：
2000
影响因子：
2.5
通讯作者：
T. Boehm
中科院分区：
文献类型：
--
作者：
M. Schorpp;T. Schlake;Darren Kreamalmeyer;P. Allen;T. Boehm
裸基因座编码 Whn，叉头/翼螺旋类的转录因子。 Whn 突变导致胸腺上皮分化失败，相应地缺乏胸腺内 T 细胞发育；在皮肤中，毛囊角质形成细胞的分化受到干扰，导致脆弱毛干的形成。在这里，我们描述了一种新型裸等位基因 nuStL 的鉴定和表征。 nuStL 编码截短的 Whn 转录因子蛋白，命名为 WhnStL，缺乏激活结构域，但保留了特征性 DNA 结合结构域。相比之下，之前描述的 Whnnu 突变蛋白缺乏这两个结构域。 nuStL/nuStL 小鼠表现出无淋巴样胸腺雏形，且缺乏外周 T 细胞，与 nu/nu 小鼠类似。在皮肤中，观察到毛发角蛋白基因 mHa1、mHa2、mHa3 和 mHa4、mHb3、mHb4、mHb5 和 mHb6 的表达受损，其模式与 nu/nu 小鼠相似：就这些毛发角蛋白基因的表达而言，两个突变等位基因都表现为亚型。然而，这两个等位基因之间的 mHa5 表达存在显着差异，mHa5 表达在 nuStL/nuStL 中降低，但在 nu/nu 小鼠中不降低。我们发现 nu/nu 小鼠中的突变 Whn 蛋白不能进入细胞核，而 nuStL/nuStL 小鼠中的突变 Whn 蛋白存在于细胞核中。因此，激活缺陷型 WhnStL 蛋白相对于 mHa5 表达的反态特征很可能是由其与 mHa5 基因顺式调控区域的其他蛋白的非生产性相互作用引起的。我们的结果表明，Whn 基因突变的分子后果可能不同，并证明了头发角蛋白基因转录控制机制的意外复杂性。开发动力 2000；218：537–543。 © 2000 Wiley-Liss, Inc.
The nude locus encodes Whn, a transcription factor of the forkhead/winged‐helix class. Mutations in Whn cause failure of differentiation of thymic epithelium with a corresponding lack of intrathymic T‐cell development; in the skin, differentiation of follicular keratinocytes is disturbed resulting, in the formation of fragile hair shafts. Here, we describe the identification and characterization of a novel nude allele, nuStL. nuStL encodes a truncated Whn transcription factor protein, designated WhnStL, lacking the activation domain but retaining the characteristic DNA binding domain. In contrast, the previously described Whnnu mutant protein lacks both domains. nuStL/nuStL mice show an alymphoid thymic rudiment and lack of peripheral T cells, similar to nu/nu mice. In the skin, impaired expression of hair keratin genes mHa1, mHa2, mHa3 and mHa4, mHb3, mHb4, mHb5, and mHb6 is observed in a pattern that parallels that of nu/nu mice: both mutant alleles behave as hypomorphs with respect to the expression of these hair keratin genes. However, a significant difference between these two alleles exists for mHa5 expression, which is reduced in nuStL/nuStL but not in nu/nu mice. We show that the mutant Whn protein in nu/nu mice cannot enter the nucleus, whereas the mutant Whn protein in nuStL/nuStL mice is present in the nucleus. The antimorphic characteristic of the activation‐deficient WhnStL protein with respect to mHa5 expression is therefore most likely caused by its non‐productive interaction with other proteins at cis‐regulatory regions of the mHa5 gene. Our results indicate that the molecular consequences of mutations of the Whn gene can be different and demonstrate an unexpected complexity of transcriptional control mechanisms of hair keratin genes. Dev Dyn 2000;218:537–543. © 2000 Wiley‐Liss, Inc.
影响因子：
4.4
作者：
SEGRE, JA;NEMHAUSER, JL;LANDER, ES
通讯作者：
LANDER, ES