Combinatorial control

The ability of the leucine zipper proteins to form heterodimers greatly expands the repertoire of DNA-binding specificities that these proteins can display. As illustrated in Figure 10.19, for example, three distinct DNA-binding specificities could, in principle, be generated from two types of monomer, while six could be created from three types of monomer and so on. This is an example of combinatorial control, in which combinations of proteins, rather than individual proteins, control a cellular process. It is one of the most important mechanisms used by eucaryotic cells to control gene expression. 

McKenna, N. and O Malley, B. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 108 465-474,2002. 

The HS7 region is composed of multiple factor binding sites some of these factors are ubiquitously expressed, whereas others are cell-specific factors, supporting the notion that the HS7 transcriptional activity is determined by a combinatorial control the combined action of tissue-restricted and ubiquitously expressed proteins. The HS7 regulatory region described in this report could either bring additional cellular... 

Patton, E. E., Willems, A. R., and Tyers, M. (1998). Combinatorial control in ubiquitin-dependent proteolysis don t Skp the F-box hypothesis. Trends Genet 14,236-43. 

Bollen M (2001) Combinatorial control of protein phosphatase-1. Trends Biochem Sci 26 426-431. 

A major advantage of this mode of regulation is that a given regulatory protein can have different effects, depending on what other proteins are present in the same cell. This phenomenon, called combinatorial control, is crucial to... 

Gajewski, K., Kim, Y., Choi, C. Y, and Schulz, R. A. (1998). Combinatorial control of Drosophila mef2 gene expression in cardiac and somatic muscle cell linet es. Dev. Genes Evol. 208 382-392. Gajewski, K., Kim, Y., Lee, Y., Olson, E., and Schulz, R. (1997). D-mefi is a target for Tinman activation during Drosophila heart development. EMBO J. 16 515-522. 

Hertel, K. J. (2008). Combinatorial control of exon recognition. J Biol Chem 283(3), 1211—1215. 

Tonks, N.K. and Neel, B.G. (2001) Combinatorial control of the specificity of protein tyrosine phosphatases. Curr.Opin.Cell Biol., 13, 182-195. 

Bessa, J., Gebelein, B., Pichaud, F., Casares, F., Mann, R.S. 2002. Combinatorial control of Drosophila eye development by Eyeless, Homothorax, and Teashirt. Genes Dev. 16, 2415-2427. 

Knockout mice and Drosophila mutants have been used to explore the roles of MRF and MEF proteins in conferring myogenic specificity in intact animals, extending the work in cell culture. These experiments demonstrated the importance of three of the MRF proteins and of MEF proteins for distinct steps in muscle development (see Figure 22-14). The function of the fourth myogenic protein, Mrf4, is not entirely clear It may be expressed later and help maintain differentiated muscle cells and by combinatorial control to ensure that only muscle-specific genes are activated. 

Combinatorial control of eukaryotic transcription. The net effect of multiple transcription factors interacting with the transcriptional initiation complex can either be gene activation or gene repression. Since some transcription factors are cell-specific in their own expression, the presence or absence of these particular transcription factors can influence rates of transcription of individual genes. 

Remenyi A, Scholer HR, Wilmanns M. Combinatorial control of gene expression. Nat Struct Mol Biol 2004 11 812-815. 

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