Sequence-specific Transcription Factors

Muliprotein complexes that do not directly bind DNA, but are recruited by sequence-specific transcription factors and mediate their capacity to activate genes (coactivators) and to repress genes (corepressors). 

Sequence-specific transcription factors often bind as multimers especially as dimers to DNA. This allows binding of mirror-imaged sequences (palindromes) in the DNA that are separated by a few spacer nucleotides. The dimerization is stabilized by hydrophobic motifs within dimerization motifs of each transcription factor molecule. Dependent on the nature of the dimerization domain and the abundance of individual transcription factors homo- or heterodimers can form and bind to palindromes with differential activity. 

The multiprotein unit that synthesize RNA by copying the sequence information from the leading strand of the DNA. Its activity is tightly controlled by phosphorylation of the C-termal domain (CTD), access to DNA and interaction by general and sequence specific transcription factors and coactivators and corepressors. 

Levine, M. and Hoey, T. (1988) Homeobox proteins as sequence-specific transcription factors. Cell 55 537-540. 

Physical (e.g., heat shock, ionizing radiation) and physiological (e.g., hypoxia) stresses, along with metabolic factors (e.g., glucose), induce specific gene expression by mechanisms involving DNA sequence specific transcription factors (Table 2.1). 

Table 2.1 Examples of DNA sequence specific transcription factors that regulate stress inducible promoters now being used in therapeutic applications. Shown are the stress inducers, transcriptional activating proteins and consensus response elements recognized by the transacting proteins...

Examples of DNA sequence specific transcription factors that regulate stress inducible 15... 

M. A. Martinez Baibas, A. Dey, S. K. Rabindian, K. Ozato, and C. Wii. Displacement of sequence-specific transcription factors from mitotic chromatin. Cefi, 83 (1), 29—38, 1995. 

Martinez-Balbas, M.A., Dey, A., Rabindran, S.K., Ozato, K., and Wu, C. (1995). Displacement of sequence-specific transcription factors from mitotic chomatin. Oil 83 29-38. 

The trans-regulatory factors that mediate the Bmp response are of obvious interest. Although smad proteins are well-known as transducers of the Bmp signal from cytoplasm to nucleus (von Bubnoff and Cho, 2001), they bind weakly to DNA and are thought to require sequence-specific transcription factors for their function. It will thus be informative to examine closely the Msx2 Bmp responsive cis-regulatory element and cognate factors. 

It is well established that DNA sequence specific transcription factors influence transcription through interactions not only with DNA, but also with co-activator and co-repressor proteins. Given the growing number of examples in which Msx proteins have been found to influence transcription without binding DNA (Catron et al., 1995 Newberry 1997 Zhou and Snead, 2000), it has become increasingly important to identify Msx2 co-factors/interacting proteins. By means of two hybrid and far western screens, as well as candidate approaches, several such molecules have been identified. 

---