TheC. elegansCBFβ homologue BRO-1 interacts with the Runx factor, RNT-1, to promote stem cell proliferation and self-renewal

• DOI: 10.1242/dev.008276
• Publication Date: 2007-10-12T08:18:18Z
• Authors: Hiroshi Kagoshima; Rachael Nimmo; Nicole Saad; Junko Tanaka; Yoshihiro Miwa; Shohei Mitani; Yuji Kohara; Alison Woollard
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Sequence Homology, Amino Acid; Stem Cells; Molecular Sequence Data; Gene Expression Regulation, Developmental; DNA; Repressor Proteins; 03 medical and health sciences; Phenotype; Mutation; Animals; Humans; Cell Lineage; Female; Amino Acid Sequence; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Sequence Alignment; Cell Proliferation; Protein Binding; Transcription Factors

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