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

In this report, we investigate the C. elegans CBF beta 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 CBF beta- 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/ CBF beta factors have oncogenic potential.