Quantitative Discrimination of MEF2 Sites

Abstract

Myocyte-specific enhancer factor 2 (MEF2) is a family of closely related transcription factors that play a key role in the differentiation of muscle tissues and are important in the muscle-specific expression of a number of genes. Given the centrality of MEF2 in muscle differentiation, regulatory regions newly determined to be muscle specific are often studied for potential MEF2 binding sites. Possible sites are often located by comparison to a homologous gene or by matching to the consensus MEF2 sequence. Enough data have accumulated that a richer description of the MEF2 binding site, a position weight matrix, can be reliably constructed and its usefulness can be assessed. It was shown that scores from such a matrix approximate MEF2 binding energy and enable recognition of naturally occurring MEF2 sites with high sensitivity and specificity. Regulation of genes via MEF2-like sites is complicated by the fact that a number of transcription factors are involved. Not only is MEF2 itself a family of proteins, but several other, nonhomologous, transcription factors overlap MEF2 in DNA-binding specificity. Thus, more quantitative methods for recognizing potential sites may help with the lengthy process of disentangling the complex regulatory circuits of muscle-specific expression.