Transcription factor MafB also known as V-maf musculoaponeurotic fibrosarcoma oncogene homolog B is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''MAFB''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. This gene maps to
chromosome 20
Chromosome 20 is one of the 23 pairs of chromosomes in humans. Chromosome 20 spans around 66 million base pairs (the building material of DNA) and represents between 2 and 2.5 percent of the total DNA in cells. Chromosome 20 was fully sequenced i ...
q11.2-q13.1, consists of a single exon and spans around 3 kb.
Function
MafB is a basic leucine zipper (
bZIP
The Basic Leucine Zipper Domain (bZIP 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 tog ...
)
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
that plays an important role in the regulation of lineage-specific
hematopoiesis
Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells ...
. The encoded nuclear protein represses
ETS1
Protein C-ets-1 is a protein that in humans is encoded by the ''ETS1'' gene. The protein encoded by this gene belongs to the ETS family of transcription factors.
Function
There are 28 ETS genes in humans and 27 in mice. They bind the DNA via ...
-mediated transcription of erythroid-specific genes in
myeloid cells.
Clinical significance
Mutations in the murine Mafb gene are responsible for the mutant mouse Kreisler (kr) that presents an abnormal segmentation of the hindbrain and exhibit hyperactive behavior, including head tossing and running in circles.
This mice dies at birth due to renal failure whereas the Mafb -/- mice dies of central apnea.
Recently,
single-nucleotide polymorphisms
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
(SNPs) near MAFB have been found associated with nonsyndromic
cleft lip and palate
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...
.
The GENEVA Cleft Consortium study, a genomewide association study involving 1,908 case-parent trios from Europe, the United States, China, Taiwan, Singapore, Korea, and the Philippines, first identified MAFB as being associated with cleft lip and/or palate with stronger
genome-wide significance
In genome-wide association studies, genome-wide significance (abbreviated GWS) is a specific threshold for determining the statistical significance of a reported association between a given single-nucleotide polymorphism (SNP) and a given trait. ...
in Asian than European populations. The difference in populations could reflect variable coverage by available markers or true allelic heterogeneity. In mouse models, Mafb mRNA and protein were detected in both craniofacial
ectoderm and neural crest-derived mesoderm between embryonic days 13.5 and 14.5; expression was strong in the epithelium around the palatal shelves and in the medial edge epithelium during palatal fusion. After fusion, Mafb expression was stronger in oral epithelium compared to mesenchymal tissue.
In addition, sequencing analysis detected a new
missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution.
Substitution of protein from DNA mutations
Missense m ...
in the Filipino population, H131Q, that was significantly more frequent in cases than in matched controls.
The gene-poor regions either side of the MAFB gene include numerous binding sites for transcription factors that are known to have a role in palate development.
[ Dixon MJ, Marazita ML, Beaty TH, Murray JC. 2011. Cleft lip and palate: understanding genetic and environmental influences. ''Nature Reviews Genetics''. 12: 167-178 ]
References
Further reading
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{{Transcription factors, g1
Transcription factors