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Advanced Drug Delivery Reviews Jul 2009Pancreatic beta-cell-specific insulin gene expression is regulated by a variety of pancreatic transcription factors and the conserved A3, C1 and E1 elements in the... (Review)
Review
Pancreatic beta-cell-specific insulin gene expression is regulated by a variety of pancreatic transcription factors and the conserved A3, C1 and E1 elements in the insulin gene enhancer region are very important for activation of insulin gene. Indeed, PDX-1 binding to the A3 element and NeuroD binding to the E1 element are crucial for insulin gene transcription. Recently, C1 element-binding transcription factor was identified as MafA, which is a basic-leucine zipper transcription factor and functions as a potent transactivator for the insulin gene. Under diabetic conditions, chronic hyperglycemia gradually deteriorates pancreatic beta-cell function, which is accompanied by decreased expression and/or DNA binding activities of MafA and PDX-1. Furthermore, MafA overexpression, together with PDX-1 and NeuroD, markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells. These results suggest that MafA plays a crucial role in pancreatic beta-cells and could be a novel therapeutic target for diabetes.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Homeodomain Proteins; Humans; Insulin; Insulin-Secreting Cells; Maf Transcription Factors, Large; Nerve Tissue Proteins; Trans-Activators; Transcriptional Activation
PubMed: 19393272
DOI: 10.1016/j.addr.2008.12.015 -
Biochemical and Biophysical Research... Apr 1998maf is a family of genes encoding bZIP transcription factors. We isolated two cellular maf-related cDNAs, maf-1 (mafB) and maf-2 (c-maf), from rat and determined the...
maf is a family of genes encoding bZIP transcription factors. We isolated two cellular maf-related cDNAs, maf-1 (mafB) and maf-2 (c-maf), from rat and determined the specificities of DNA binding and heterodimer formation. Although both Mafs strongly bind to MARE, the consensus Maf recognition sequence (MARE, -TGCTGACTCAGCA-), originally identified by v-Maf protein Maf-1, recognizes a number of sequences containing only the first half of the MARE, -GCTGAC-. On the other hand, no such consensus short sequence could be determined for Maf-2. We determined the specificities of heterodimer formation with all members of the Jun and Fos family. In contrast to v-Maf which forms heterodimers with all Jun and Fos proteins, Maf-1 heterodimerizes with all four Fos proteins, but not at all with the three Jun proteins. Maf-2 heterodimerizes with c-Fos. We have also found that heterodimer formation of Maf-2 with c-Fos dramatically changes the specificity of DNA binding and trans-activation activity from that of the Maf-2 homodimer. These results show that Maf-1 and Maf-2 have significantly different properties and they might have different target genes and functions, in spite of the similarity of their bZip domain structure.
Topics: Animals; Avian Proteins; Basic-Leucine Zipper Transcription Factors; Consensus Sequence; DNA-Binding Proteins; Dimerization; G-Box Binding Factors; MafB Transcription Factor; Oligodeoxyribonucleotides; Oncogene Proteins; Protein Conformation; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Proto-Oncogene Proteins c-maf; Rats; Trans-Activators; Transcription Factors; Transcriptional Activation
PubMed: 9571165
DOI: 10.1006/bbrc.1998.8447 -
Molecular and Cellular Biology Apr 1995The maf oncogene encodes a bZip nuclear protein which recognizes sequences related to an AP-1 site either as a homodimer or as heterodimers with Fos and Jun. We describe... (Comparative Study)
Comparative Study
The maf oncogene encodes a bZip nuclear protein which recognizes sequences related to an AP-1 site either as a homodimer or as heterodimers with Fos and Jun. We describe here a novel maf-related gene, mafG, which shows extensive homology with two other maf-related genes, mafK and mafF. These three maf-related genes encode small basic-leucine zipper proteins lacking the trans-activator domain of v-Maf. Bacterially expressed small Maf proteins bind to DNA as homodimers with a sequence recognition profile that is virtually identical to that of v-Maf. As we have previously described, the three small Maf proteins also dimerize with the large subunit of NF-E2 (p45) to form an erythroid cell-specific transcription factor, NF-E2, which has distinct DNA-binding specificity. This study shows that the small Maf proteins can also dimerize among themselves and with Fos and a newly identified p45-related molecule (Ech) but not with v-Maf or Jun. Although the small Maf proteins preferentially recognize the consensus NF-E2 sequence as heterodimers with either NF-E2 p45, Ech, or Fos, these heterodimers seemed to be different in their transactivation potentials. Coexpression of Fos and small Mafs could not activate a promoter with tandem repeats of the NF-E2 site. These results raise the possibility that tissue-specific gene expression and differentiation of erythroid cells are regulated by competition among Fos, NF-E2 p45, and Ech for small Maf proteins and for binding sites.
Topics: Amino Acid Sequence; Animals; Base Sequence; Chickens; Consensus Sequence; DNA-Binding Proteins; Erythroid-Specific DNA-Binding Factors; Gene Expression Regulation; Genomic Library; Models, Genetic; Molecular Sequence Data; NF-E2 Transcription Factor; NF-E2 Transcription Factor, p45 Subunit; Oncogene Protein v-maf; Oncogene Proteins, Viral; Protein Binding; Protein Conformation; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Proto-Oncogene Proteins c-maf; Repressor Proteins; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Suppression, Genetic; Transcription Factors; Viral Proteins
PubMed: 7891713
DOI: 10.1128/MCB.15.4.2180 -
Molecular and Cellular Biology Aug 2022The transcription factor MafB plays an essential role in -cell differentiation during the embryonic stage in rodents. Although MafB disappears from -cells after birth,...
The transcription factor MafB plays an essential role in -cell differentiation during the embryonic stage in rodents. Although MafB disappears from -cells after birth, it has been reported that MafB can be evoked in -cells and is involved in insulin-cell number and islet architecture maintenance in adult mice under diabetic conditions. However, the underlying mechanism by which MafB protects -cells remains unknown. To elucidate this, we performed RNA sequencing using an inducible diabetes model ( mice) that we previously generated. We found that the deletion of can induce -cell dedifferentiation, characterized by the upregulation of dedifferentiation markers, and as well as several -cell-disallowed genes, and by the downregulation of mature -cell markers, and . However, there is no re-expression of well-known progenitor cell markers, and . Further, the appearance of ALDH1A3 cells and the disappearance of UCN3 cells also verify the -cell dedifferentiation state. Collectively, our results suggest that MafB can maintain -cell identity under certain pathological conditions in adult mice, providing novel insight into the role of MafB in -cell identity maintenance.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Diabetes Mellitus; Insulin; Insulin-Secreting Cells; Maf Transcription Factors, Large; MafB Transcription Factor; Mice; Nerve Tissue Proteins
PubMed: 35862726
DOI: 10.1128/mcb.00541-21 -
Cell Apr 2002The T helper lymphocyte is responsible for orchestrating an appropriate immune response to pathogens. To do so, it has evolved into two specialized subsets that direct... (Review)
Review
The T helper lymphocyte is responsible for orchestrating an appropriate immune response to pathogens. To do so, it has evolved into two specialized subsets that direct type 1 and type 2 immunity. Here, we discuss the genetic programs that control lineage commitment of progenitor T helper cells along each of these pathways.
Topics: Animals; Cell Differentiation; Cell Lineage; Cytokines; DNA-Binding Proteins; GATA3 Transcription Factor; Gene Expression Regulation; Humans; NFATC Transcription Factors; Nuclear Proteins; Protein Processing, Post-Translational; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-maf; STAT6 Transcription Factor; T-Box Domain Proteins; T-Lymphocytes; Trans-Activators; Transcription Factors; Transcription, Genetic
PubMed: 11983157
DOI: 10.1016/s0092-8674(02)00705-5 -
Trends in Endocrinology and Metabolism:... Sep 2011Analyses in mouse models have revealed crucial roles for MafA (musculoaponeurotic fibrosarcoma oncogene family A) and MafB in islet β cells, with MafB being required... (Review)
Review
Analyses in mouse models have revealed crucial roles for MafA (musculoaponeurotic fibrosarcoma oncogene family A) and MafB in islet β cells, with MafB being required during development and MafA in adults. These two closely related transcription factors regulate many genes essential for glucose sensing and insulin secretion in a cooperative and sequential manner. Significantly, the switch from MafB to MafA expression also appears to be vital for functional maturation of β cells produced by human embryonic stem (hES) cell differentiation. This review summarizes the discovery, distribution, and function of MafA and MafB in rodent pancreatic β cells, and describes some key questions regarding their importance to β cells.
Topics: Animals; Embryonic Stem Cells; Glucose; Insulin; Insulin-Secreting Cells; Maf Transcription Factors, Large; MafB Transcription Factor; Mice; Models, Animal
PubMed: 21719305
DOI: 10.1016/j.tem.2011.05.003 -
Blood Sep 1999The transcriptional mechanisms that drive colony-forming unit granulocyte-macrophage (CFU-GM) myeloid progenitors to differentiate into cells of either the granulocytic...
The transcriptional mechanisms that drive colony-forming unit granulocyte-macrophage (CFU-GM) myeloid progenitors to differentiate into cells of either the granulocytic or monocytic lineage are not fully understood. We have shown that the c-Maf and c-Myb transcription factors physically interact in myeloid cells to form inhibitory complexes that hinder transactivation of c-Myb target genes through direct binding to Myb consensus sites. These complexes arise in a developmentally regulated pattern, peaking at the promyelocyte stage, or in cell model systems, appearing soon after the induction of monocytic differentiation. We wished to determine if this developmentally related interaction is a consequence of myeloid differentiation or an intrinsic differentiating stimulus. Because the elevated Myb:Maf status seen in differentiating cells can be recapitulated by overexpression of c-Maf in myeloid cell lines, we inducibly expressed the c-Maf cDNA in 2 bipotent human myeloid progenitor cells. Elevated levels of c-Maf protein led to marked increases in Myb:Maf complexes and the accumulation of monocyte/macrophage cells, followed by eventual programmed cell death. Analysis of targets that could mediate these phenotypic changes indicated that c-Maf likely plays a key role in myeloid cell development through dual mechanisms; inhibition of a select set of c-Myb regulated targets, such as Bcl-2 and CD13/APN, coupled with the activation of as yet undefined differentiation-promoting genes.
Topics: Apoptosis; Cell Differentiation; DNA-Binding Proteins; Gene Expression Regulation; HL-60 Cells; Hematopoietic Stem Cells; Humans; Leukopoiesis; Monocytes; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-maf; Proto-Oncogene Proteins c-myb; Trans-Activators
PubMed: 10477683
DOI: No ID Found -
Biology of Reproduction Oct 2021Testis differentiation is initiated when Sry in pre-Sertoli cells directs the gonad toward a male-specific fate. Sertoli cells are essential for testis development, but...
Testis differentiation is initiated when Sry in pre-Sertoli cells directs the gonad toward a male-specific fate. Sertoli cells are essential for testis development, but cell types within the interstitial compartment, such as immune and endothelial cells, are also critical for organ formation. Our previous work implicated macrophages in fetal testis morphogenesis, but little is known about genes underlying immune cell development during organogenesis. Here, we examine the role of the immune-associated genes Mafb and Maf in mouse fetal gonad development, and we demonstrate that deletion of these genes leads to aberrant hematopoiesis manifested by supernumerary gonadal monocytes. Mafb; Maf double knockout embryos underwent initial gonadal sex determination normally, but exhibited testicular hypervascularization, testis cord formation defects, Leydig cell deficit, and a reduced number of germ cells. In general, Mafb and Maf alone were dispensable for gonad development; however, when both genes were deleted, we observed significant defects in testicular morphogenesis, indicating that Mafb and Maf work redundantly during testis differentiation. These results demonstrate previously unappreciated roles for Mafb and Maf in immune and vascular development and highlight the importance of interstitial cells in gonadal differentiation.
Topics: Animals; Embryo, Mammalian; MafB Transcription Factor; Male; Mice; Myeloid Cells; Organogenesis; Proto-Oncogene Proteins c-maf; Testis
PubMed: 34007995
DOI: 10.1093/biolre/ioab098 -
Developmental Dynamics : An Official... Aug 2011Bone morphogenetic protein (BMP) signals are essential for lens development. However, the temporal requirement of BMP activity during early events of lens development...
Bone morphogenetic protein (BMP) signals are essential for lens development. However, the temporal requirement of BMP activity during early events of lens development has remained elusive. To investigate this question, we have used gain- and loss-of-function analyses in chick explant and intact embryo assays. Here, we show that BMP activity is both required and sufficient to induce L-Maf expression, whereas the onset of δ-crystallin and initial elongation of primary lens fibre cells are BMP-independent. Moreover, before lens placode formation and L-Maf onset, but not after, prospective lens placodal cells can switch to an olfactory placodal fate in response to decreased BMP activity. In addition, L-Maf is sufficient to up-regulate δ-crystallin independent of BMP signals. Taken together, these results show that before L-Maf induction BMP activity is required for lens specification, whereas after L-Maf up-regulation, the early differentiation of primary lens fibre cells occurs independent of BMP signals.
Topics: Animals; Bone Morphogenetic Proteins; Cell Differentiation; Chick Embryo; Eye Proteins; Gene Expression Regulation, Developmental; Homeodomain Proteins; Keratins; Lens, Crystalline; Maf Transcription Factors; PAX6 Transcription Factor; Paired Box Transcription Factors; Repressor Proteins; SOXB1 Transcription Factors; Signal Transduction; Smad Proteins; delta-Crystallins
PubMed: 21761477
DOI: 10.1002/dvdy.22692 -
Gene Expression Patterns : GEP Jan 2004Maf proteins are basic-leucine zipper transcription factors belonging to the AP1 superfamily. Several developmental processes require Maf proteins yet, the redundancy or... (Comparative Study)
Comparative Study
Maf proteins are basic-leucine zipper transcription factors belonging to the AP1 superfamily. Several developmental processes require Maf proteins yet, the redundancy or complementarity of their respective roles in common processes has been only partially investigated. We present for the first time a complete comparative analysis of maf gene expression patterns in vertebrates. Expression of c-maf, mafB/kreisler, mafA/L-maf, mafF, mafG and mafK was analyzed by whole-mount in situ hybridization within chick embryos and their extraembryonic tissues ranging from embryonic day (E) 1 to 7. We carefully examined the extent of overlap between distinct maf genes and report that the developing lens, kidney, pancreas and apoptotic zones of limb buds show sustained co-expression of large maf genes. Small maf genes also exhibit overlap, for example in the dermomyotome. We also describe so far unidentified sites of maf gene expression. mafA is found in the developing neural tube and dorsal root ganglia. c-maf hybridization is detected in the neuroretina, the notochord and the endothelium of extraembryonic blood vessels.
Topics: Animals; Chick Embryo; DNA-Binding Proteins; Gastrula; Gene Expression Profiling; Gene Expression Regulation, Developmental; In Situ Hybridization; Limb Buds; MafF Transcription Factor; MafK Transcription Factor; Mesoderm; Nuclear Proteins; Pancreas; Peripheral Nervous System; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-maf; Repressor Proteins; Retina; Spinal Cord
PubMed: 14678826
DOI: 10.1016/s1567-133x(03)00152-2