We detected a novel nuclear protein, MRF, that binds to multiple sites on the modulator which is located upstream of the human cytomegalovirus major immediate early gene enhancer. The expression of MRF is differentiation specific; the DNA binding activity is present in nuclear extracts from undifferentiated Tera-2 and THP-1 cells, but significantly reduced after these cells are induced to differentiate. In undifferentiated cells the enhancer activity is repressed by the modulator and upon differentiation the enhancer becomes active. Competitive binding assays demonstrate that MRF requires the presence of multiple A+T stretches for binding to DNA, rather than binding to a specific DNA sequence. Mutations of these stretches in the modulator reduce the binding activity of MRF, as well as the repressing activity on the enhancer. These results suggest that MRF may act as a repressor of enhancer function. We propose that MRF binds over the entire modulator and exerts repressor activity.

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About 40% of the world’s population is overweight or obese and exist at risk of developing type 2 diabetes mellitus (T2D). Obesity is a leading pathogenic factor for developing insulin resistance (IR). It is well established that IR and a progressive decline in functional β-cell mass are hallmarks of developing T2D. In order to mitigate the global prevalence of T2D, we must carefully select the appropriate animal models to explore the cellular and molecular mechanisms of T2D, and to optimize novel therapeutics for their safe use in humans. Flavonoids, a group of polyphenols, have drawn great interest for their various health benefits, and have been identified in naturally occurring anti-diabetic compounds. Results from many clinical and animal studies demonstrate that dietary intake of flavonoids might prove helpful in preventing T2D. In this review, we discuss the currently available rodent animal models of T2D and analyze the advantages, the limitations of each T2D model, and highlight the potential anti-diabetic effects of flavonoids as well as the mechanisms of their actions.