PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression : implications for the pathology of Rieger syndrome
(2001) In Journal of Cell Biology 152(3). p.545-552- Abstract
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... (More)
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-1-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.
(Less)
- author
- Hjalt, Tord A. LU ; Amendt, Brad A. and Murray, Jeffrey C.
- publishing date
- 2001-02-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Abnormalities, Multiple/genetics, Animals, Base Sequence, Cell Line, Chromatin/metabolism, Cricetinae, Ehlers-Danlos Syndrome/genetics, Gene Expression Regulation, Enzymologic, Genes, Reporter/genetics, Homeodomain Proteins/genetics, Humans, Mice, Molecular Sequence Data, Multigene Family/genetics, Nuclear Proteins, Paired Box Transcription Factors, Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics, Recombinant Fusion Proteins/metabolism, Regulatory Sequences, Nucleic Acid/genetics, Syndrome, Transcription Factors/genetics
- in
- Journal of Cell Biology
- volume
- 152
- issue
- 3
- pages
- 8 pages
- publisher
- Rockefeller University Press
- external identifiers
-
- scopus:0035809197
- pmid:11157981
- ISSN
- 0021-9525
- DOI
- 10.1083/jcb.152.3.545
- language
- English
- LU publication?
- no
- id
- 55b25b78-f9d9-4b55-99a4-fc533531ac9e
- date added to LUP
- 2023-11-16 11:32:16
- date last changed
- 2024-01-14 04:13:11
@article{55b25b78-f9d9-4b55-99a4-fc533531ac9e,
abstract = {{<p>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-1-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.</p>}},
author = {{Hjalt, Tord A. and Amendt, Brad A. and Murray, Jeffrey C.}},
issn = {{0021-9525}},
keywords = {{Abnormalities, Multiple/genetics; Animals; Base Sequence; Cell Line; Chromatin/metabolism; Cricetinae; Ehlers-Danlos Syndrome/genetics; Gene Expression Regulation, Enzymologic; Genes, Reporter/genetics; Homeodomain Proteins/genetics; Humans; Mice; Molecular Sequence Data; Multigene Family/genetics; Nuclear Proteins; Paired Box Transcription Factors; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics; Recombinant Fusion Proteins/metabolism; Regulatory Sequences, Nucleic Acid/genetics; Syndrome; Transcription Factors/genetics}},
language = {{eng}},
month = {{02}},
number = {{3}},
pages = {{545--552}},
publisher = {{Rockefeller University Press}},
series = {{Journal of Cell Biology}},
title = {{PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression : implications for the pathology of Rieger syndrome}},
url = {{http://dx.doi.org/10.1083/jcb.152.3.545}},
doi = {{10.1083/jcb.152.3.545}},
volume = {{152}},
year = {{2001}},
}