Aberrant expression of the P2 promoter-specific transcript Runx1 in epiphyseal cartilage of Trps1-null mice
Aberrant expression of the P2 promoter-specific transcript Runx1 in epiphyseal cartilage of Trps1-null mice
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DOI：
10.1016/j.yexmp.2010.11.010
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发表时间：
2011-04-01
影响因子：
3.6
通讯作者：
Muragaki, Yasuteru
中科院分区：
文献类型：
--
作者：
Kanno, Seiji;Gui, Ting;Muragaki, Yasuteru
毛发-鼻-趾骨综合征（TRPS）是由编码加塔型转录抑制因子的Trps 1基因突变引起的常染色体显性遗传骨骼疾病。为了研究作用于Trps 1下游的基因，我们使用ATDC 5细胞进行了DNA阵列。从DNA阵列中鉴定的靶基因之一是Runx 1，它是造血所必需的，并且像Runx 2一样在软骨形成中起着重要作用。荧光素酶启动子试验和染色体免疫沉淀试验表明，Runx 1在小鼠骺软骨中的表达被抑制Trps 1结合到P2启动子的加塔结构域; Runx 1基因的两个启动子的近端片段。通过原位杂交检测Trps 1基因敲除小鼠生长板软骨细胞中P2转录本的异常表达。总之，Trps 1与Runx 1基因的P2启动子结合并下调Runx 1表达，这是正常软骨形成所必需的。(C)2010年爱思唯尔公司All rights reserved.
Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant skeletal disorder caused by mutations of the Trps1 gene, which encodes a GATA type transcriptional repressor. To investigate the genes that act downstream of Trps1, we performed a DNA array using ATDC5 cells. One of the target genes identified from the DNA array was Runx1, which is essential for hematopoiesis and like Runx2 plays a significant role in chondrogenesis. A luciferase promoter assay and a chromosome immunoprecipitation assay showed that Runx1 expression in mouse epiphyseal cartilage was repressed by Trps1 binding to the GATA domain of the P2 promoter; the proximal segment of two promoters of the Runx1 gene. The aberrant expression of P2 transcripts was detected in growth plate chondrocytes from Trps1-null mice by in situ hybridization. In conclusion, Trps1 binds to the P2 promoter of the Runx1 gene and down-regulates Runx1 expression, which is necessary for normal cartilage formation. (C) 2010 Elsevier Inc. All rights reserved.