The C elegans CBF beta homolog, BRO-1, regulates the proliferation, differentiation and specification of the stem cell-like seam cell lineages

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The RUNX/CBF heterodimeric transcription factor plays an important role in regulating cell proliferation and differentiation in a variety of developmental contexts. Aberrant function of Runx and CBF has been causally related to the development of various diseases, including acute myeloid leukemia, gastric cancer and cleidocranial dysplasia. The underlying mechanism of the RUNX/CBF beta complex in regulation of cell proliferation is still poorly defined. In this study, we demonstrate that the Caenorhabditis elegans CBF beta homolog, bro-1, is essential for the proliferation, differentiation and specification of a row of stem cell-like lineages, called seam cells. BRO-1 forms complex with the C. elegans RUNX homolog, RNT-1, and augments the DNA-binding activity of RNT-1. The RNT-1/BRO-1 complex directly interacts with the C. elegans Groucho homolog, UNC-37, whose loss of function mutations display similar defects in the proliferation of seam cells as those of bro-1 and rnt-1 mutants. Additionally, the defects in seam cell division in bro-1 mutants are substantially rescued by the inactivation of the negative regulators of the G1 to S phase cell cycle progression, including the lin-35 Rb, fzr-1 Cdh1 and cki-1 CIP homologs. Our studies indicate that the transcriptional repression activity of the RNT-1/BRO-1 complex regulates the G1 to S cell cycle progression during seam cell division. (C) 2007 Elsevier Inc. All rights reserved.

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CBF beta runx groucho seam cell c. elegans BINDING-FACTOR-BETA MULTIPLE CHROMOSOMAL TRANSLOCATIONS DEPENDENT KINASE INHIBITOR FETAL LIVER HEMATOPOIESIS CAENORHABDITIS-ELEGANS TRANSCRIPTION FACTOR RUNT DOMAIN DEVELOPMENTAL REGULATION BONE-FORMATION GENE