SUMMARY PARAGRAPH for MIG1
MIG1 was first identified as a Multicopy Inhibitor of Galactose gene expression (1). Mig1p is a Zinc-finger protein, of the Cys2His2 type, that binds specifically to DNA with a GC-rich consensus sequence and a flanking AT sequence (3). It is thought that a major function of Mig1p is to repress the transcription of genes whose expression is shut off when glucose is present, such as those encoding enzymes for utilization of the sugars maltose, sucrose, or galactose (7, 4). In addition to Mig1p, other Cys2His2 type zinc finger containing DNA-binding repressor proteins such as Mig2p and Mig3p are also involved (8, 7, 4). It has also been shown that in some contexts, Mig1p functions as a transcriptional activator (4, 5).
According to the long-standing recruitment model, during repressing conditions, i.e. in the presence of glucose, cytoplasmically located Mig1p is dephosphorylated by the Reg1p-Glc7p protein phosphatase complex and then imported into the nucleus (4). In the nucleus, it binds to promoters of glucose-repressed genes where it recruits the Cyc8p-Tup1p corepressor complex (4). When cells become limited for glucose, Mig1p is phosphorylated by the Snf1 kinase complex, composed of the Snf1 kinase catalytic subunit, the gamma subunit Snf4p, and a beta subunit encoded by SIP1, SIP2, or GAL83 (5). Upon phosphorylation, Mig1p is exported from the nucleus by the nuclear exportin Msn5p (4). However, nuclear export does not completely account for derepression of glucose-repressed genes; thus in this model least one other mechanism is involved in the inactiviation of the Mig1p repressor (4).
A newer alternative model, called reverse recruitment, postulates that promoters regulated by many transcription factors, including Mig1p, are recruited to "Gene Expression Machines", or GEMs, which are located at the nuclear periphery and are associated with a nuclear pore complex and other complexes involved in mRNA processing and export (5). In this model, DNA binding factors do not diffuse through the nucleus, but rather bind to the promoters at the nuclear pore in both repressing and activating conditions. Phosphorylation of DNA-bound regulators, such as Mig1p, may result in subtle conformational changes which control whether the factor functions as a repressor or an activator (5).
Last updated: 2007-02-16