Expression pattern, regulation, and biological role of runt domain transcription factor, run, in Caenorhabditis elegans.
The Caenorhabditis elegans run gene encodes a Runt domain factor. Runx1, Runx2, and Runx3 are the three known mammalian homologs of run. Runx1, which plays an essential role in hematopoiesis, has been identified at the breakpoint of chromosome translocations that are responsible for human leukemia. Runx2 plays an essential role in osteogenesis, and inactivation of one allele of Runx2 is responsible for the human disease cleidocranial dysplasia. To understand the role of run in C. elegans, we used transgenic run::GFP reporter constructs and a double-stranded RNA-mediated interference method. The expression of run was detected as early as the bean stage exclusively in the nuclei of seam hypodermal cells and lasted until the L3 stage. At the larval stage, expression of run was additionally detected in intestinal cells. The regulatory elements responsible for the postembryonic hypodermal seam cells and intestinal cells were separately located within a 7.2-kb-long intron region. This is the first report demonstrating that an intron region is essential for stage-specific and cell type-specific expression of a C. elegans gene. RNA interference analysis targeting the run gene resulted in an early larva-lethal phenotype, with apparent malformation of the hypodermis and intestine. These results suggest that run is involved in the development of a functional hypodermis and gut in C. elegans. The highly conserved role of the Runt domain transcription factor in gut development during evolution from nematodes to mammals is discussed.
Nam
Seunghee
S
Department of Biology, Yonsei University, Seoul 120-749, South Korea.
Jin
Yun-Hye
YH
Li
Qing-Lin
QL
Lee
Kwang-Youl
KY
Jeong
Goo-Bo
GB
Ito
Yoshiaki
Y
Lee
Junho
J
Bae
Suk-Chul
SC
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D017930:Genes, Reporter; D006801:Humans; D007438:Introns; D009363:Neoplasm Proteins; D010641:Phenotype; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; C493729:Runx3 protein, human; D014157:Transcription Factors