Currently must of our studies focus on the biology of two transcription factors, Runx1 and Runx3, that belong to the RUNX gene family. The RUNX genes arose early in evolution and maintained extensive structural similarities in mammals.
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| Fig. 1: RUNX gene phylogeny. A. RUNX genes are highly conserved in evolution down to sponges. The number of RUNX genes is indicated in parentheses and promoter usage is designated as P1 and P2. B. Genomic organization of the human RUNX genes (common exons are shown in similar color). Chromosomal localization and conserved neighboring genes (CLIC and DSCR) are depicted. |
RUNX1 resides on chromosome 21, and we address its potential involvement in DS leukemia (see the “Chromosome 21 Connection”).
RUNX3 resides on chromosome 1 at 1p36.1 in a region known to be involved in several important human diseases.
 Fig. 2: Regulation of gene expression by tissue-specific transcription factors involves both turning on and turning off transcription of target genes. The RUNT domain transcription factors (TF) RUNX elicit repression of target genes by tethering the co-repressor Groucho/TLE to a subset of target promoters. |
The RUNX are master regulators of lineage specific gene expression in several important developmental pathways. One of the exciting questions in molecular biology is how differential gene expression patterns are established and maintained during development. While our lab is molecular biology-oriented, our notion has been that it is not sufficient to study the biochemical mechanisms in cell culture, and that in depth understanding entails experiments in animal models. To this end we investigate the biology of Runx1 and Runx3, both in vitro at the molecular level and in vivo using genetically modified mouse models.
 Fig. 3: Even though the RUNX TF recognize the same DNA-motif and regulate their target genes through interaction with common transcriptional co-activators or co-repressors, the functional overlaps are minor, and each RUNX has a distinct subset of biological functions. How is this tissue specific expression of RUNX in a distinct subset of cell types and at defined time windows during development attained? How are these transcriptional regulators are regulated? We employ a series of overlapping BACs spanning large (i.e. hundreds Kb) of Runx3 and Runx1 loci to identify and characterize the long-range regulatory elements mediating tissue and stage specific expression of Runx1 and Runx3 during development and in adults. |
Updated: 09/05/2012 14:32:02 Contact E-mail: Yoram.Groner@weizmann.ac.il