DNA binding specificity

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. 

Figure 10.19 Heterodimerization of leucine zipper proteins can alter their DNA-binding specificity. Leucine zipper homodimers bind to symmetric DNA sequences, as shown In the left-hand and center drawings. These two proteins recognize different DNA sequences, as indicated by the red and blue regions in the DNA. The two different monomers can combine to form a heterodimer that recognizes a hybrid DNA sequence, composed of one red and one blue region.

Dessain, S., Gross, C. T., Kuziora, M. A., and McGinnis, W. (1992). Antp-type homeo-domains have distinct DNA binding specificities that correlate with their different regulatory functions in embryos. EMBO J. 11 991-1002. 

Treisman, J., Gonczy, P., Vashishtha, M., Harris, E., and Desplan, C. (1989). A single amino acid can determine the DNA binding specificity of homeodomain proteins. Cell 59 553-562. 

Bulyk, M. L., Huang, X., Choo, Y., and Church, G. M. (2001). Exploring the DNA-binding specificities of zinc fingers with DNA microarrays. Proc. Natl. Acad. Sci. USA 98, 7158-7163. 

Hai, T. and Curran, T. Cross-family dimerization of transcription factors Fos/Iun and ATF/CREB alters DNA binding specificity. Proc. Natl Acad. Sci. U.S.A. 88 3720-3724, 1991. 

WILLIAMS, C.E., GROTEWOLD, E., Differences between plant and animal Myb domains are fundamental for DNA binding activity and chimeric Myb domains have novel DNA-binding specificities, J. Biol. Chem., 1997, 272, 563-571. 

Wisniewski, J.R., Szewczuk, Z., Petry, I., Schwanbeck, R., and Renner, U. (1999) Constitutive phosphorylation of the acidic tails of the high mobility group 1 proteins by casein kinase II alters their conformation, stability, and DNA binding specificity. J Biol. Chem. 274, 20116-20122. 

Fig. 1.38. Formation of homo- and heterodimeric transcription factors and the specificy of DNA-binding. Shown are two different helrx-loop-helix proteins, which bind as homodimers (a, b) to the each of their cognate palindromic DNA elements (drawn as arrows). The two homodimers display different DNA-binding specificity. The heterodimerization (c) of the two proteins creates a complex that recognizes a hybrid DNA element.

Tomic, S., Nilsson, L., Wade, R. C. (2000) Nuclear receptor-DNA binding specificity a COMBINE and Free-Wilson QSAR analysis. JMed Chem 43(9), 1780-1792. 

Rebar, E. J and Pabo, C O. (1994) Zinc finger phage affinity selection of fingers with new DNA-binding specificities. Science 263, 671-673... 

Although an isolated homeodomain can fold correctly and bind DNA with a specificity similar to that of the intact proteins, it is believed that the precise DNA-binding specificity is modulated by other regions of the protein. Protein-protein interactions may also have a role in modulating many homeodomain-DNA interactions. For example, the... 

Pollock, R. and Treisman, R. (1990) A sensitive method for the determination of protein-DNA binding specificities. Nucleic Acids Res., 18,6197-6204. 

Swanson HI, Chan WK, Bradfield CA. 1995. DNA binding specificities and pairing rules of the Ah receptor, ARNT, and SIM proteins. J Biol Chem 270 26292-26302. 

Maiti A, Roy S. Switching DNA-binding specificity by unnatural amino acid substitution. Nucleic Acids Res. 2005 33 5896-5903. 

DNA-binding specificities of zinc fingers with DNA microarrays. 

Inspection of the complete E. coli genome sequence reveals two sites within 500 bp of the primary operator site that approximate the sequence of the operator. Other lac repressor dimers can bind to these sites, particularly when aided by cooperative interactions with the lac repressor dimer at the primary operator site. No other sites that closely match sequence of the lac operator site are present in the rest of the E. coli genome sequence. Thus, the DNA-binding specificity of the lac repressor is sufficient to specify a nearly unique site within the E. coli genome. 

P.A. Moore, et al. A human TATA binding protein-related protein with altered DNA binding specificity inhibits transcription from multiple promoters and activators. Mol. Cell Biol. 19 (1999) 7610-20. 

M. Strubin and K. Struhl. Yeast and human TFIID with altered DNA-binding specificity for TATA elements. Cell 68 (1992) 721-30. 

Oumouna, M., L. Jaso-Friedmann and D.L. Evans. Activation of nonspecific cytotoxic cells (NCC) with synthetic oligodeoxynucleotides and bacterial genomic DNA binding, specificity and identification of unique immunostimulatory motifs. Dev. Comp. Immunol. 26 257-269, 2002. 

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