FC0024
GCN4 transcription factor  -  Basic transcriptional machinery

Biological function
GCN4 is a transcription factor that is responsible for the activation of more than 30 genes. It binds and recognize the DNA sequence: 5’-TGA[CG]TCA-3’.

Domain organization/sequence features
GCN4 contains a 89aa DNA-binding domain and an acidic transcriptional activation region.

Structural evidence
Proteolysis experiments show that the transactivation region is unstructured with some local ordering.

Biochemical evidence
Truncation and internal deletion experiments on the 87-152 segment show that a significant portion of the activation region could be deleted without a loss of activity. A 25aa region (107-131) is the minimum length with detectable activity and for full function a 32 aa region (107-138) is needed. Progressive deletion induced a gradual change in activity. The small, step-wise activity reductions are consistent with a composition of small units, which act in a synergistic manner.

Structure/Mechanism
Analysis of GCN4 interactions with the Mediator of RNAPII indicate that different activation regions are gene-specific and surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions.

Mechanism category
tethering

Significance
Fuzziness and the corresponding interaction ambiguity enables activation of different genes by different activation regions. Owing to the lack of structural constraints these can also act in a synergistic manner and provide gradual regulation of transcriptional activity.

Further reading
20308326