The MADS-Box Family of Transcription Factors

Abstract

The MADS-box family of transcription factors has been defined on the basis of primary sequence similarity amongst numerous proteins from a diverse range of eukaryotic organisms including yeasts, plants, insects, amphibians and mammals. The MADS-box is a conserved motif found within the DNA-binding domains of these proteins and the name refers to four of the originally identified members: MCM1, AG, DEFA and SRF. Several proteins within this family have significant biological roles. For example, the human serum-response factor (SRF) is involved in co-ordinating transcription of the protooncogene c-fos, whilst MCM1 is central to the transcriptional control of cell-type specific genes and the pheromone response in the yeast Saccharomyces cerevisiae. The RSRF/MEF2 proteins comprise a sub-family of this class of transcription factors which are key components in muscle-specific gene regulation. Moreover, in plants, MADS-box proteins such as AG, DEFA and GLO play fundamental roles during flower development. The MADS-box is a contiguous conserved sequence of 56 amino acids, of which 9 are identical in all family members described so far. Several members have been shown to form dimers and consequently two functional regions within the MADS-box have been defined. The N-terminal half is the major determinant of DNA-binding specificity whilst the C-terminal half is necessary for dimerisation. This organisation allows the potential formation of numerous proteins, with subtly different DNA-binding specificities, from a limited number of genes by heterodimerisation between different MADS-box proteins. The majority of MADS-box proteins bind similar sites based on the consensus sequence CC(A/T)6GG although each protein apparently possesses a distinct binding specificity. Moreover, several MADS-box proteins specifically recruit other transcription factors into multi-component regulatory complexes. Such interactions with other proteins appears to be a common theme within this family and play a pivotal role in the regulation of target genes.

APETALA1 and SEPALLATA3 interact to promote flower development

“…These observations, together with the accumulating data suggesting that MADS-box gene products typically inter-act with other proteins (Davies et al, 1996;Egea-Cortines et al, 1999;Fan et al, 1997;Shore and Sharrocks, 1995), suggested that AP1 and CAL may share a common set of protein partners, and that additional proteins may interact speci®cally with AP1. Using the yeast two-hybrid assay, we found that AP1 and CAL can each interact with a shared set of proteins, including SEP3, SOC1, SVP and AGL24.…”

“…Remarkably, with the exception of the AP2 gene, all the other organ-identity genes belong to the extended family of MADS-box genes, a family that is known to include more than 44 distinct sequences in Arabidopsis (Alvarez- Buylla et al, 2000a;Davies and Schwarz-Sommer, 1994;Purugganan et al, 1995;Rounsley et al, 1995). MADS-domain proteins, well characterized in yeast (MCM1, Ammererer, 1990) and mammals (SRF, Norman et al, 1988), form dimers that bind to DNA and form ternary complexes with many unrelated proteins (Lamb and McKnight, 1991;Shore and Sharrocks, 1995). A number of studies have shown that heterodimers and ternary complexes of plant MADS-domain proteins can occur and, given the overlapping expression pattern of numerous MADS-box genes, such interactions greatly increase the regulatory complexity of MADS-box genes (Davies et al, 1996;Egea-Cortines et al, 1999;Fan et al, 1997).…”

“…A number of studies have shown that heterodimers and ternary complexes of plant MADS-domain proteins can occur and, given the overlapping expression pattern of numerous MADS-box genes, such interactions greatly increase the regulatory complexity of MADS-box genes (Davies et al, 1996;Egea-Cortines et al, 1999;Fan et al, 1997). The regulatory speci®city of these genes is achieved through protein±protein interactions and not through different intrinsic DNA-binding speci®cities Shore and Sharrocks, 1995). MADS-box proteins are composed of four different domains, designated M, I, K and C. The MADS (M) domain is highly conserved among these proteins, and is responsible for binding to DNA in addition to its participation in homodimer formation of some proteins.…”

Identification of a New Hybrid Serum Response Factor and Myocyte Enhancer Factor 2-binding Element in MyoD Enhancer Required for MyoD Expression during Myogenesis

“…First, the two proteins have overlapping binding sequences in MyoD-SMB. Second, no interaction is possible between two different members of the MADS-box family (for review, see Shore and Sharrocks, 1995), and we found no evidence of interaction (by coimmunoprecipitation) in differentiated myotube extracts (our unpublished observations). Third, SRF and MEF2 proteins compete for binding to MyoD-SMB element ( Figure 4A).…”

“…Because SRF interacts with DNA by point contacts with the helix minor groove and MEF2 with the major groove of DNA (Mueller and Nordheim, 1991;Wynne and Treisman, 1992), both factors could, in principle, occupy the SMB site simultaneously. However, interactions between the two members of the MADS-box family have not been described previously (our unpublished data; Shore and Sharrocks, 1995). The steric hindrance of high molecular weight (MW) complexes associated with either SRF (L'honore et al, 2003) or MEF2 (ϳ600 kDa; our unpublished observation) suggests a mutually exclusive binding of SRF-and MEF2-containing complexes to SMB element.…”