Human homologue of maid: A dominant inhibitory helix-loop-helix protein associated with liver-specific gene expression
Human homologue of maid: A dominant inhibitory helix-loop-helix protein associated with liver-specific gene expression
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DOI：
10.1053/jhep.2000.9092
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发表时间：
2000-08-01
期刊：
影响因子：
13.5
通讯作者：
Thorgeirsson, SS
中科院分区：
文献类型：
--
作者：
Terai, S;Aoki, H;Thorgeirsson, SS
转录螺旋-环-螺旋 (HLH) 家族。调节蛋白是许多发育过程中的关键调节因子。 I 类 HLH 蛋白（例如 E12）普遍表达。 II 类 HLH 蛋白，例如 MyoD，以组织特异性方式表达，I 类和 II 类异二聚体可以与 E-box (CANNTG) 结合并调节胚胎细胞的谱系定型。为了寻找可能在肝脏发育过程中发挥控制作用的 E12 蛋白伴侣，我们使用来自人胎儿肝脏的表达互补 DNA 文库进行了酵母 2 杂交筛选。分离并表征了一种新型显性抑制性 HLH 因子，称为 HHM（人类女仆同源物）。 HHM 在结构上与 Id 家族相关，在脑、垂体、肺、心脏、胎盘、胎儿肝脏和骨髓中高表达。 HHM 在体外和哺乳动物细胞中与 E12 发生物理相互作用。比较 HHM 和 Id2 对 E12/MyoD 二聚体与 E-box 元件结合的显着抑制作用，发现 HHM 的抑制较弱。然而，HHM 而不是 Id2 特异性抑制肝核因子 4 (HNF4) 启动子诱导的荧光素酶基因激活。 HHM 在干细胞驱动的肝脏再生过程中短暂表达，此时肝细胞的早期嗜碱性病灶开始出现。这些结果表明 HHM 是一种新型显性抑制性 HLH 蛋白，可能调节肝脏特异性基因表达。
The helix-loop-helix (HLH) family of transcriptional. regulatory proteins are key regulators in numerous developmental processes. The class I HLH proteins, such as E12 are ubiquitously expressed. Class II HLH proteins, such as MyoD, are expressed in a tissue-specific manner, Class I and II heterodimers can bind to E-boxes (CANNTG) and regulate lineage commitments of embryonic cells. In an attempt to identify partners for the E12 protein that may exert control during liver development, we performed the yeast 2-hybrid screen using an expression complementary DNA library from human fetal liver. A novel dominant inhibitory HLH factor, designated HHM (human homologue of maid), was isolated and characterized. HHM is structurally related to the Id family and was highly expressed in brain, pituitary gland, lung, heart, placenta, fetal liver, and bone marrow. HHM physically interacted with E12 in vitro and in mammalian cells. Comparison of the dominant inhibitory effects of HHM and Id2 on the binding of E12/MyoD dimer to an E-box element revealed a weaker inhibition by HHM. However, HHM but not Id2 specifically inhibited the luciferase gene activation induced by hepatic nuclear factor 4 (HNF4) promoter. The HHM was transiently expressed during stem-cell-driven regeneration of the liver at the stage in which the early basophilic foci of hepatocytes started to appear. These results suggest that HHM is a novel type of dominant inhibitory HLH protein that might modulate liver-specific gene expression.