GAL4

The Gal4 transcription factor is a positive regulator of gene expression of galactose-induced genes as are GAL1, GAL2, GAL7, GAL10, and MEL1 .

The Gal4 protein represents a large fungal family of transcription factors, Gal4 family, which includes over 50 members in the yeast Saccharomyces cerevisiae e.g. Oaf1, Pip2, Pdr1, Pdr3, Leu3 .

Two executive domains, DNA binding and activation domains,

provide key function of the Gal4 protein conforming to the most of transcription factors.

The DNA binding domain

localised to the N-terminus,

belongs to the Zn(2)-C6 fungal family, which forms a Zn – cysteines thiolate cluster .

The Gal4 activation domain

localised to the C-terminus,

belongs to the nine amino acids TransActivation Domain family, 9aaTAD,

together with Oaf1, Pip2, Pdr1, Pdr3, but also p53, E2A, MLL .

Galactose induces Gal4 mediated transcription albeit Glucose causes severe repression .

As a part of the Gal4 regulation, inhibitory protein Gal80 recognises and binds to the Gal4 region (853-874 aa)

encompassing the Gal4 activation domain 9aaTAD .

The inhibitory protein Gal80 is sequestered by regulatory protein Gal3 in Galactose dependent manner .

The Gal4 loss-of-function mutant gal4-64 (1-852 aa, deletion of the Gal4 C-terminal 29 aa) lost both interaction with Gal80 and activation function .

In the Gal4 reverted mutant Gal4C-62 mutant , a sequence (QTAY N AFMN) with the 9aaTAD pattern emerged and restored activation function of the Gal4 protein (doi: https://doi.org/10.1101/110882).

The activation domain Gal4 is inhibited by C-terminal domain in some Gal4 constructs (doi: https://doi.org/10.1101/110882).

A subunit of the 26 S proteasome Sug2 regulatory protein has a molecular and functional interaction with Gal4 function .

The Gal4 activation function is mediated by MED15 (Gal11) .

The Gal4 protein interacts also with other mediators of transcription as are Tra1 , TAF9 , and SAGA/MED15 complex (http://mcb.asm.org/content/25/1/114/F8.large.jpg).

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