Kang Ho Chul, Chae Ji Hyung, Kim Beom Sue, Han Su Youne, Kim Sung-Hyun, Auh Chung-Kyoon, Yang Sung-Il, Kim Chul Geun
Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 133-791, Korea.
Mol Cells. 2004 Jun 30;17(3):454-61.
CP2 is a member of a family of transcription factors that regulate genes involved in events from early development to terminal differentiation. In an effort to understand how it selects its target genes we carried out a database search, and located several CP2 binding motifs in the promoter region of bone morphogenetic protein-4 (BMP4). BMP4 is a key regulator of cell fate and body patterning throughout development. For the CP2 binding motifs in BMP4 promoter region to be relevant in vivo, CP2 and BMP4 should be expressed together. We found that CP2b and CP2c, two potent transcriptional activators, are expressed in a manner similar to BMP4 during osteoblast differentiation of C3H10T1/2 cells. In in vitro assays, the CP2 proteins bound to two CP2 binding motifs (-715 to -676 and -147 to -118) in the BMP4 promoter, and luciferase reporter assays indicated that this binding was essential for transcription of BMP4 during osteoblast differentiation. Taken together, our data indicate that CP2b and CP2c play important roles during bone development by activating BMP4 transcription.
CP2是一个转录因子家族的成员,该家族调控从早期发育到终末分化过程中涉及的基因。为了了解它如何选择其靶基因,我们进行了数据库搜索,并在骨形态发生蛋白4(BMP4)的启动子区域定位了几个CP2结合基序。BMP4是整个发育过程中细胞命运和身体模式形成的关键调节因子。为了使BMP4启动子区域中的CP2结合基序在体内具有相关性,CP2和BMP4应该共同表达。我们发现,在C3H10T1/2细胞成骨细胞分化过程中,两种强效转录激活因子CP2b和CP2c的表达方式与BMP4相似。在体外实验中,CP2蛋白与BMP4启动子中的两个CP2结合基序(-715至-676和-147至-118)结合,荧光素酶报告基因实验表明这种结合对于成骨细胞分化过程中BMP4的转录至关重要。综上所述,我们的数据表明CP2b和CP2c通过激活BMP4转录在骨骼发育过程中发挥重要作用。