Activation and repression the role of co-factors

To determine whether HOX proteins, with or without their partners, act as repressors or activators of transcription requires access to direct targets in a given system. This has been approached in two ways through the construction and testing of artificial HOX-responsive enhancers, and the identification of naturally occurring target elements. Both approaches confirm a role for HOX proteins in activation and repression (JCrasnow et al., 1989 Johnson and Krasnow, 1990  

Pinsonneault et al., 1997 Jacobs et al., 1999 Ferretti et al., 2000 White et al., 2000). This duality is verified by genetic studies showing, for example, that UBX represses Antp (Peifer and Wieschaus, 1990), but activates dpp (Capovilla et al., 1994 Sun et al., 1995). More controversial is whether activation is the exclusive jurisdiction of PBC-HOX heterodimers. 

Despite these persuasive arguments, some recent observations oppose a strict EXD-switch. First, HOX proteins have been shown to activate transcription through sites that do not mediate co-operative DNA-binding with PBC members. Thus, an enhancer of the fly 1.28 gene is positively regulated by four DFD binding sites that do not permit co-operative association with EXD (Pederson et al., 2000). Because the activity of this enhancer was not examined in an exd null background, however, it is possible that EXD exerts an effect nonetheless. It could be proposed, therefore, 

In another example, a HOX-EXD binding site in an enhancer of the fly forkhead (JkK) gene mediates activation by complexes of EXD with SCR, ANTP or UBX, but 

In a mammalian system, transcriptional repression has also been ascribed to PBC-HOX heterodimers. Multimers of a PBX-HOX co-operative binding site (TGATTGAT) decrease reporter gene activity in transfected cells by comparison to an otherwise identical reporter bearing HOX monomer binding sites (Saleh et al., 2000b). However, at least some of this repression could be due to PBX homodimers and PBX MEIS or PBX-PREP heterodimers that are likely to bind multimerized PBC-HOX sites. Two instances of EXD-dependent but HOX-independent repression could be mediated by comparable EXD homodimers or EXD HTH heterodimers (Rauskolb and Wieschaus, 1994 Pinsonneault et al., 1997). 

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