首页> 外文期刊>Molecular and Cellular Biology >Repression by HoxA7 is mediated by the homeodomain and the modulatory action of its N-terminal-arm residues.
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Repression by HoxA7 is mediated by the homeodomain and the modulatory action of its N-terminal-arm residues.

机译:HoxA7的抑制作用是由同源域及其N末端臂残基的调节作用介导的。

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Hox genes encode homeodomain-containing proteins that are presumed to control spatial patterning during murine embryogenesis through their actions as transcriptional regulatory proteins. In this study, we have investigated the transcriptional function of a prototypic member of this family, HoxA7. We demonstrate that HoxA7 function as a potent transcriptional repressor and that its action as such requires several domains, including both activator and repressor regions. The repressor regions are contained within the homeodomain and a C-terminal acidic region, both of which are well conserved among members of the Hox family. Accordingly, we show that two other members of this family also function as repressors, although they vary in their relative repressor potency. Finally, we explore the novel observation that the homeodomain of HoxA7 functions as a transcriptional repressor domain. We show that the homeodomain compared with two other DNA-binding domains, is unique in its ability to function as a repressor domain and that repression requires conserved residues, in helix III. We further show that residues in the N-terminal arm of the homeodomain contribute to the differential repressor actions of various Hox proteins. These findings demonstrate that the transcriptional function of HoxA7 and possibility of Hox proteins in general is determined by their unique combination of conserved and nonconserved regions as well as through the complex actions of their homeodomains.
机译:Hox基因编码含有同源结构域的蛋白质,推测它们通过作为转录调节蛋白的作用来控制鼠胚发生期间的空间模式。在这项研究中,我们调查了该家族的原型成员HoxA7的转录功能。我们证明,HoxA7作为有效的转录阻遏物,其作用本身需要几个域,包括激活区和阻遏区。阻遏物区域包含在同源域和C末端酸性区域内,两者在Hox家族成员中都非常保守。因此,我们表明该家族的另外两个成员也起着阻遏物的作用,尽管它们的相对阻遏物效力不同。最后,我们探讨了HoxA7同源域起转录抑制域功能的新颖观察。我们显示,与两个其他DNA结合结构域相比,该同源结构域在其功能上起着阻遏物结构域的作用是独特的,而该阻遏作用需要螺旋III中的保守残基。我们进一步表明,同源域N末端臂中的残基有助于各种Hox蛋白的差异阻遏物作用。这些发现表明,HoxA7的转录功能和Hox蛋白的可能性通常由保守区和非保守区的独特组合以及其同源域的复杂作用决定。

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