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First published online October 12, 2007
doi: 10.1242/10.1242/dev.008276


Development 134, 3905-3915 (2007)
Published by The Company of Biologists 2007


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The C. elegans CBFß homologue BRO-1 interacts with the Runx factor, RNT-1, to promote stem cell proliferation and self-renewal

Hiroshi Kagoshima1,*,{dagger}, Rachael Nimmo2,*, Nicole Saad2, Junko Tanaka3, Yoshihiro Miwa3,4, Shohei Mitani5, Yuji Kohara1 and Alison Woollard2,{dagger}

1 Genome Biology Laboratory, National Institute of Genetics, Mishima 411-8560, Japan.
2 Genetics Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
3 Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8577, Japan.
4 Precursory Research and Embryonic Science and Technology (PRESTO), JST, Okazaki 444-8585, Japan.
5 Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo 162-8666, Japan.

{dagger} Author for correspondence (e-mail: hkagoshi{at}lab.nig.ac.jp; alison.woollard{at}bioch.ox.ac.uk)

Accepted 20 August 2007

In this report, we investigate the C. elegans CBFß homologue, BRO-1. bro-1 mutants have a similar male-specific sensory ray loss phenotype to rnt-1 (the C. elegans homologue of the mammalian CBFß-interacting Runx factors), caused by failed cell divisions in the seam lineages. Our studies indicate that BRO-1 and RNT-1 form a cell proliferation-promoting complex, and that BRO-1 increases both the affinity and specificity of RNT-1-DNA interactions. Overexpression of bro-1, like rnt-1, leads to an expansion of seam cell number and co-overexpression of bro-1 and rnt-1 results in massive seam cell hyperplasia. Finally, we find that BRO-1 appears to act independently of RNT-1 in certain situations. These studies provide new insights into the function and regulation of this important cancer-associated DNA-binding complex in stem cells and support the view that Runx/CBFß factors have oncogenic potential.

Key words: C. elegans, CBFß, Stem cell, Proliferation, Self-renewal, Runx


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© The Company of Biologists Ltd 2007