Transcription factor MafG is a bZip Maf transcription factor protein that in humans is encoded by the MAFG gene. [5] [6]
MafG is one of the small Maf proteins, which are basic region and leucine zipper (bZIP)-type transcription factors. The HUGO Gene Nomenclature Committee-approved gene name of MAFG is “v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G”.
MafG was first cloned and identified in chicken in 1995 as a new member of the small Maf (sMaf) genes. [5] MAFG has been identified in many vertebrates, including humans. There are three functionally redundant sMaf proteins in vertebrates, MafF, MafG, and MafK. [6] [7]
MafG has a bZIP structure that consists of a basic region for DNA binding and a leucine zipper structure for dimer formation. [5] Similar to other sMafs, MafG lacks any canonical transcriptional activation domains. [5]
MAFG is broadly but differentially expressed in various tissues. MAFG expression was detected in all 16 tissues examined by the human BodyMap Project, but relatively abundant in lung, lymph node, skeletal muscle and thyroid tissues. [8] MafG gene expression is induced by oxidative stresses, such as hydrogen peroxide and electrophilic compounds. [9] [10] Mouse Mafg gene is induced by Nrf2-sMaf heterodimers through an antioxidant response element (ARE) at the promoter proximal region. [10] In response to bile acids, mouse Mafg gene is induced by the nuclear receptor, FXR (Farnesoid X receptor). [11]
Because of sequence similarity, no functional differences have been observed among the sMafs in terms of their bZIP structures. sMafs form homodimers by themselves and heterodimers with other specific bZIP transcription factors, such as CNC (cap 'n' collar) proteins [p45 NF-E2 (NFE2), Nrf1 (NFE2L1), Nrf2 (NFE2L2), and Nrf3 (NFE2L3)] [12] [13] [14] [15] and Bach proteins (BACH1 and BACH2). [16]
sMaf homodimers bind to a palindromic DNA sequence called the Maf recognition element (MARE: TGCTGACTCAGCA) and its related sequences. [7] [17] Structural analyses have demonstrated that the basic region of a Maf factor recognizes the flanking GC sequences. [18] By contrast, CNC-sMaf or Bach-sMaf heterodimers preferentially bind to DNA sequences (RTGA(C/G)NNNGC: R=A or G) that are slightly different from MARE. [19] The latter DNA sequences have been recognized as antioxidant/electrophile response elements [20] [21] or NF-E2-binding motifs [22] [23] to which Nrf2-sMaf heterodimers and p45 NF-E2-sMaf heterodimer bind, respectively. It has been proposed that the latter sequences should be classified as CNC-sMaf-binding elements (CsMBEs). [19]
It has also been reported that sMafs form heterodimers with other bZIP transcription factors, such as c-Jun and c-Fos. [24]
sMafs regulate different target genes depending on their partners. For instance, the p45-NF-E2-sMaf heterodimer regulate genes responsible for platelet production. [12] [25] [26] Nrf2-sMaf heterodimer regulates a battery of cytoprotective genes, such as antioxidant/xenobiotic metabolizing enzyme genes. [14] [27] The Bach1-sMaf heterodimer regulates the heme oxygenase-1 gene. [16] In particular, it has been reported that Bach1-MafG heterodimers participate in the hypermethylation of genes with CpG island promoters in certain types of cancers. [28] The contribution of individual sMafs to the transcriptional regulation of their target genes has not yet been well examined.
Loss of sMafs results in disease-like phenotypes as summarized in table below. Mice lacking MafG exhibit mild neuronal phenotype and mild thrombocytopenia. [25] However, mice lacking Mafg and one allele of Mafk (Mafg−/−::Mafk+/−) exhibit more severe neuronal phenotypes, severe thrombocytopenia and cataracts. [29] [30] Mice lacking MafG and MafK (Mafg−/−::Mafk−/− ) die in the perinatal stage. [31] Finally, mice lacking MafF, MafG and MafK are embryonic lethal. [32] Embryonic fibroblasts that are derived from Maff−/−::Mafg−/−::Mafk−/− mice fail to activate Nrf2-dependent cytoprotective genes in response to stress. [27]
| Genotype | Mouse Phenotype | ||
|---|---|---|---|
| Maff | Mafg | Mafk | |
| −/− | Mild motor ataxia, mild thrombocytopenia [25] | ||
| −/− | +/− | Severe motor ataxia, progressive neuronal degeneration, severe thrombocytopenia, and cataract [29] [30] | |
| −/− | −/− | More severe neuronal phenotypes, and perinatal lethal [31] | |
| −/− | +/− | −/− | No severe abnormality [32] (Fertile) |
| −/− | −/− | −/− | Growth retardation, fetal liver hypoplasia, and lethal around embryonic day, 13.5 [32] |
| +/− (heterozygote), −/− (homozygote), blank (wild-type) | |||
In addition, accumulating evidence suggests that as partners of CNC and Bach proteins, sMafs are involved in the onset and progression of various human diseases, including neurodegeneration, arteriosclerosis and cancer.
 | The 2016 version of this article was updated by an external expert under a dual publication model. The corresponding academic peer reviewed article was published in Gene and can be cited as: Fumiki Katsuoka, Masayuki Yamamoto (4 April 2016). "Small Maf proteins (MafF, MafG, MafK): History, structure and function". Gene . Gene Wiki Review Series. 586 (2): 197–205. doi:10.1016/J.GENE.2016.03.058. ISSN 0378-1119. PMC 4911266 . PMID 27058431. Wikidata Q37014084. |
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Transcription factor Maf also known as proto-oncogene c-Maf or V-maf musculoaponeurotic fibrosarcoma oncogene homolog is a transcription factor that in humans is encoded by the MAF gene.
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The Basic Leucine Zipper Domain is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties and the leucine zipper that is required to hold together (dimerize) two DNA binding regions. The DNA binding region comprises a number of basic amino acids such as arginine and lysine. Proteins containing this domain are transcription factors.
bZIP Maf is a domain found in Maf transcription factor proteins. It contains a leucine zipper (bZIP) domain, which mediates the transcription factor's dimerization and DNA binding properties. The Maf extended homology region (EHR) is present at the N-terminus of the protein. This region exists only within the Maf family and allows the family to recognize longer DNA motifs than other leucine zippers. These motifs are termed the Maf recognition element (MARE) and is 13 or 14 base pairs long. In particular, the two residues at the beginning of helix H2 are positioned to recognise the flanking region of the DNA. Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF2-E2 transcription factor.
Small Maf proteins are basic region leucine zipper-type transcription factors that can bind to DNA and regulate gene regulation. There are three small Maf (sMaf) proteins, namely MafF, MafG, and MafK, in vertebrates. HUGO Gene Nomenclature Committee (HGNC)-approved gene names of MAFF, MAFG and MAFK are “v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F, G, and K”, respectively.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
