PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression: Implications for the pathology of Rieger syndrome

被引:71
作者
Hjalt, TA
Amendt, BA
Murray, JC
机构
[1] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA
[2] Univ Tulsa, Dept Biol Sci, Tulsa, OK 74104 USA
关键词
PITX2; PLOD; Rieger; Ehlers-Danlos; promoter;
D O I
10.1083/jcb.152.3.545
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The Rieger syndrome is an autosomal dominant disease characterized by ocular, craniofacial, and umbilical defects. Patients have mutations in PITX2, a paired-bicoid homeobox gene, also involved in left/right polarity determination. In this study we have identified a family of genes for enzymes responsible for hydroxylizing lysines in collagens as one group of likely cognate targets of PITX2 transcriptional regulation. The mouse procollagen lysyl hydroxylase (Plod)-2 gene was enriched for by chromatin precipitation using a PITX2/Pitx2-specific antibody. Plod-2, as well as the human PLOD-1 promoters, contains multiple bicoid (PITX2) binding elements. We show these elements to bind PITX2 specifically in vitro. The PLOD-1 promoter induces the expression of a luciferase reporter gene in the presence of PITX2 in cotransfection experiments. The Rieger syndrome causing PITX2 mutant T68P fails to induce PLOD-l-luciferase. Mutations and rearrangements in PLOD-1 are known to be prevalent in patients with Ehlers-Danlos syndrome, kyphoscoliosis type (type VI [EDVI]). Several of the same organ systems are involved in Rieger syndrome and EDVI.
引用
收藏
页码:545 / 552
页数:8
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