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I attended a seminar about neurogenesis that presented results for PAX6 as an important TF that contains 3 domains with very distinct patterns of downstream expression. The speaker ended up saying that PAX6 can be considered as 3 TFs in one protein, acting independently in different situations:

Relative roles of the different Pax6 domains for pancreatic alpha cell development

Does anybody know of more examples like this?

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interesting - I have heard of 'generic' transcription factors that act on many genes via common sequence motifs (the CCAAT-enhancer-binding-proteins, for instance), but not factors that actually have different motifs with different downstream effects. I'm also interested in this. –  Luke Jun 1 '12 at 13:06

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The NF-κB family of transcription factors is very modular, with different combinations having different effects. The active (nuclear, DNA-bound) TF is a dimer, composed variously of RelA/p65, RelB, c-rel, NFKB1/p50, and/or NFKB2/p52 subunits. For example, the "canonical" p65/p50 dimer is activated in response to stimulants like TNF-α (tumor necrosis factor alpha, released in response to inflammatory signals like the presence of pathogens) and LPS (lipopolysaccharide from the cell walls of Gram-negative bacteria), while the RelB/p52 dimer plays an important role in the development of B cells (the immune system component that produces antibodies). The AP-1 transcription factor is also heterodimeric, containing proteins from the Jun, Fos, JDP, and ATF families, and there are numerous other examples of multimeric transcription factor complexes. This recent article in Nature Immunology (disclaimer: I was not involved in that research) shows DNA sequence-specific binding by different NF-κB dimers.

Polymerism in general, and dimerism in particular, are quite common modes of transcriptional activation and regulation. The large number of ways in which a relatively small number of transcription factors can be combined allows for the exquisite control of genes, responding to a huge variety of cellular situations. Unfortunately, it also means that mutations in key, common components can result in transformation, unrestricted growth, and the generation of tumors.

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There was a paper published in Cell last year that has shown that the binding motif of a Hox transcription factor will change depending on whether there's a co-factor bound to the Hox.

link to paper

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