Expression Pattern, Regulation, and Biological Role of Runt Domain Transcription Factor, run, in Caenorhabditis elegans

Abstract

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.

Homologs of RUNX and CBFβ/PEBP2β in C. elegans

“…The space between the RNT-1-coding gene and the gene located upstream of rnt-1 is fairly small, which suggests that either the promoter region of the rnt-1 gene is very small or that the big intron might be important in its transcription. Subsequent analysis supported the latter possibility (Nam et al, 2002).…”

“…For example, while the three mammalian RUNX genes have very similar gene structures, their expression patterns are distinct and reflect their disparate biological functions. The nematode RNT-1 gene was shown to be expressed exclusively in the hypodermis and the intestine of hermaphrodite animals as shown by GFP reporter assays (Nam et al, 2002). Since it is believed that the hypodermis and the digestive system may be the most primitive organs in the metazoan anatomy, the expression pattern of RNT-1 suggests that it may be close to being the prototype of the RUNX proteins (Nam et al, 2002).…”

“…The nematode RNT-1 gene was shown to be expressed exclusively in the hypodermis and the intestine of hermaphrodite animals as shown by GFP reporter assays (Nam et al, 2002). Since it is believed that the hypodermis and the digestive system may be the most primitive organs in the metazoan anatomy, the expression pattern of RNT-1 suggests that it may be close to being the prototype of the RUNX proteins (Nam et al, 2002). Consistent with this is that a mammalian homolog of rnt-1, RUNX3, is mainly expressed in the epithelial cells of the gastrointestinal tract as well as in other tissues, and knockout mice lacking RUNX3 expression show severe malfunctioning of the gastrointestinal tract .…”

“…While the mammalian RUNX proteins are expressed in distinct tissues, the nematode RNT-1 is expressed exclusively in the hypodermis and the intestine (Nam et al, 2002). An interesting feature of the RNT-1 expression pattern is that it is expressed in a stagespecific manner.…”

“…Recently, we reported the existence of a single gene encoding a RUNX homolog in the nematode (Bae and Lee, 2000). We also showed that this gene has an evolutionarily conserved function (Nam et al, 2002). While the study of the nematode RUNX gene is still in its infancy, it is worthwhile to summarize the current understanding of the nematode RUNX gene and its functions and to discuss future research directions.…”