Regulation of Id2 expression by CCAAT/enhancer binding protein beta.
Regulation of Id2 expression by CCAAT/enhancer binding protein beta.
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DOI：
10.1093/nar/gki339
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发表时间：
2005
影响因子：
14.9
通讯作者：
Yokota Y
中科院分区：
文献类型：
--
作者：
Karaya K;Mori S;Kimoto H;Shima Y;Tsuji Y;Kurooka H;Akira S;Yokota Y
缺乏Id 2（碱性螺旋-环-螺旋（bHLH）转录因子的负调节因子）的小鼠，由于妊娠期间小叶肺泡发育受损而表现出泌乳缺陷，与缺乏CCAAT增强子结合蛋白（C/EBP）β的小鼠相似。在这里，我们表明Id 2是C/EBPβ的直接靶点。利用C/EBPβ与人雌激素受体配体结合域的融合蛋白（C/EBPβ-ERT）系统将C/EBPβ转位到细胞核中，证明了内源性Id 2表达的快速诱导。在报告基因分析中，观察到C/EBPβ对Id 2启动子的反式激活，并且在2.3kb Id 2启动子区域中发现的三个潜在的C/EBPβ结合位点中，最近的元件负责反式激活。电泳迁移率变动分析（EMSA）鉴定该元件为C/EBPβ结合的核心序列。染色质免疫沉淀（ChIP）进一步证实了C/EBPβ在Id 2启动子区的存在。北方印迹显示，在性交后10天（d.p.c.），C/EBPβ缺陷乳腺中Id 2表达降低，与野生型乳腺相比。因此，我们的数据表明，Id 2是C/EBPβ的直接靶点，并提供了对妊娠期间乳腺发育的分子机制的深入了解。
Mice deficient for Id2, a negative regulator of basic helix–loop–helix (bHLH) transcription factors, exhibit a defect in lactation due to impaired lobuloalveolar development during pregnancy, similar to the mice lacking the CCAAT enhancer binding protein (C/EBP) β. Here, we show that Id2 is a direct target of C/EBPβ. Translocation of C/EBPβ into the nucleus, which was achieved by using a system utilizing the fusion protein between C/EBPβ and the ligand-binding domain of the human estrogen receptor (C/EBPβ-ERT), demonstrated the rapid induction of endogenous Id2 expression. In reporter assays, transactivation of the Id2 promoter by C/EBPβ was observed and, among three potential C/EBPβ binding sites found in the 2.3 kb Id2 promoter region, the most proximal element was responsible for the transactivation. Electrophoretic mobility shift assay (EMSA) identified this element as a core sequence to which C/EBPβ binds. Chromatin immunoprecipitation (ChIP) furthermore confirmed the presence of C/EBPβ in the Id2 promoter region. Northern blotting showed that Id2 expression in C/EBPβ-deficient mammary glands was reduced at 10 days post coitus (d.p.c.), compared with that in wild-type mammary glands. Thus, our data demonstrate that Id2 is a direct target of C/EBPβ and provide insight into molecular mechanisms underlying mammary gland development during pregnancy.
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影响因子：
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作者：
AKIRA, S;ISSHIKI, H;KISHIMOTO, T
通讯作者：
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