Aberrant expression of the P2 promoter-specific transcript Runx1 in epiphyseal cartilage of Trps1-null mice.
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.
First Department of Pathology, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan.
Seiji
S
Kanno
Ting
T
Gui
Shunji
S
Itoh
Zhibo
Z
Gai
Yujing
Y
Sun
Kosuke
K
Oikawa
Munehito
M
Yoshida
Yasuteru
Y
Muragaki
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D020219:Chondrogenesis / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004838:Epiphyses / Q000378:metabolism* / Q000473:pathology; D050980:GATA Transcription Factors / Q000172:deficiency* / Q000378:metabolism; D006132:Growth Plate / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D014158:Transcription, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D050980:GATA Transcription Factors; D012333:RNA, Messenger; D012097:Repressor Proteins; C493726:Runx1 protein, mouse; C525953:Trps1 protein, mouse; D008156:Luciferases