Worm Breeder's Gazette 15(4): 38 (October 1, 1998)
These abstracts should not be cited in bibliographies. Material
contained herein should be treated as personal communication and
should be cited as such only with the consent of the author.
The (only?) C. elegans runt gene
Thomas R. Bürglin
Biozentrum der Universität Basel, Klingelbergstrasse 70,
4056 Basel, Switzerland
The Runt gene family is a new family of heteromeric
DNA binding transcription factors. Recent work has revealed that members
of this family play important roles in embryonic development of sea
urchin, segmentation of Drosophila, and hematopoiesis and osteoblast
differntiation in mouse and human.
The heteromeric complex consists of two
subunits, a DNA binding subunit aand its partner subunit b.
The a subunit
binds directly to a specific DNA sequence (PuCCPuCAG [Pu=A/G]) while theb subunit
associates with ato form a heterodimer that has a greater affinity for DNA. The asubunit shares a region of high homology, termed the Runt domain (Fig.
1), with the products of the Drosophila segmentation gene runt and
the human acute myeloid leukemia-related gene AML1. A series of
biochemical analyses revealed that the Runt domain is sufficient for both
functions of the asubunit: DNA binding and heterodimerization with the bsubunit.
In mammals, there are 3 types of asubunits, aA,aB and aC.
Targeted disruption of aA
in mouse results in a complete lack of ossification in their skeletal systems.
The human homolog of aB,
AML1, is known as the most frequent target of chromosomal translocations
associated with leukemia, and targeted mice lacking AML1 showed
no fetal liver hematopoiesis. aB
has thus proved to be essential for hematopoiesis of all lineages.
We found a C. elegans homolog of
runt by searching in the C. elegans databases, which we propose
to call rnt-1. We made a promoter-gfp-lacZ reporter construct to examine
the temporal and spatial expression pattern. We observed gfp expression
in the hypodermis, the seam and probably their precursor cells starting
from the 2-fold stage embryo to adult. This result implied that rnt-1 might
have quite different functions in different organisms, which contrasts
with the high sequence conservation. Moreover, so far no bsubunit gene has been found in C.
elegans; this subunit has important regulatory functions for the Runt
domain. To elucidate the function of rnt-1 in worms, we are going to do
RNAi experiments and screen knock-out mutant libraries. This should give
us new insights into the function of this gene family.
: :: .* : :.** ***.**:: .* *: * *.*
. :::* .: ::.:**:*************:.* *:* : : * :*: ..**:******:.*
Fig. 1 Alignment of the Runt domains.
h: human; m: mouse; D.m. Drosophila melanogaster;
S.p. sea urchin.