Negative Regulation of β Enolase Gene Transcription in Embryonic Muscle Is Dependent upon a Zinc Finger Factor That Binds to the G-rich Box within the Muscle-specific Enhancer

Abstract

We have previously identified a muscle-specific enhancer within the first intron of the human ␤ enolase gene. Present in this enhancer are an A/T-rich box that binds MEF-2 protein(s) and a G-rich box (AGTGGGG-GAGGGGGCTGCG) that interacts with ubiquitously expressed factors. Both elements are required for tissuespecific expression of the gene in skeletal muscle cells. Here, we report the identification and characterization of a Kruppel-like zinc finger protein, termed ␤ enolase repressor factor 1, that binds in a sequence-specific manner to the G-rich box and functions as a repressor of the ␤ enolase gene transcription in transient transfection assays. Using fusion polypeptides of ␤ enolase repressor factor 1 and the yeast GAL4 DNA-binding domain, we have identified an amino-terminal region responsible for the transcriptional repression activity, whereas a carboxyl-terminal region was shown to contain a potential transcriptional activation domain. The expression of this protein decreases in developing skeletal muscles, correlating with lack of binding activity in nuclear extract from adult skeletal tissue, in which novel binding activities have been detected. These results suggest that in addition to the identified factor, which functionally acts as a negative regulator and is enriched in embryonic muscle, the G-rich box binds other factors, presumably exerting a positive control on transcription. The interplay between factors that repress or activate transcription may constitute a developmentally regulated mechanism that modulates ␤ enolase gene expression in skeletal muscle.

Novel murine clonal cell lines either express slow or mixed (fast and slow) muscle markers following differentiation in vitro

“…A small number of transcription factors have been recently identified that could be implicated in directing the phenotype of striated muscle fibers. They are as diverse as SIX1, for the specification of fast-glycolytic myofibers (Grifone et al, 2004), BERF1 that inhibits ␤-enolase expression in slow-oxidative myofibers (Passantino et al, 1998), PPAR␦ implicated in mitochondrial oxidative metabolism (Feige et al, 2006) and HIF-1␣ involved in the response to hypoxia and controlling glycolytic metabolism (Semenza, 1999). Work is in progress in our laboratory designed to manipulate the expression of such factors in the 9.…”

A gene signature of 8 genes could identify the risk of recurrence and progression in Dukes' B colon cancer patients

“…It has been shown that ZNF148 binds to GC-rich DNA elements in a variety of promoters involved in growth regulation (23)(24)(25). Moreover, for the rat pituitary adenoma cell line GH4, Bai and Merchant (26) showed that elevated expression of ZNF148 inhibits cell proliferation and promotes growth arrest through stabilization of the p53 protein.…”

Down-regulation of rat mitochondrial branched-chain 2-oxoacid dehydrogenase kinase gene expression by glucocorticoids

“…Both repressor and enhancer elements have been shown to be present in the first introns of many genes [31][32][33][34][35]. However, there were no significant differences in promoter activities between constructs k128\j264 and k128\j37, with and without intron 1 respectively ( Figure 4B).…”