Psychiatry related information on Mdfi

• This mechanism of active transcriptional repression distinguishes ZEB from other negative regulators of myogenesis (Id, Twist and I-mfa) that inhibit muscle differentiation by simply binding and inactivating myogenic factors [1].

High impact information on Mdfi

• I-mf associates with MyoD family members and retains them in the cytoplasm by masking their nuclear localization signals [2].
• We postulate that I-mf plays an important role in the patterning of the somite early in development [2].
• In contrast, I-mfa did not interfere with the activity of the bHLH protein Hand1, a positive regulator of giant cell differentiation [3].
• I-mfa interacted with the bHLH protein Mash2, a negative regulator of trophoblast giant cell formation, and inhibited its transcriptional activity in cell culture [3].
• Our results indicate that I-mfa plays an important role in trophoblast and chondrogenic differentiation by negatively regulating a subset of lineage-restricted bHLH proteins [3].

Biological context of Mdfi

• We demonstrate that I-mf inhibits the transactivation activity of the MyoD family and represses myogenesis [2].
• The bHLH-repressor protein I-mfa binds to MyoD family members, inhibits their activity, and blocks their nuclear import and binding to DNA [3].
• Requirement of the mouse I-mfa gene for placental development and skeletal patterning [3].
• In situ hybridization analysis demonstrated that mouse I-mfa was highly expressed in extraembryonic lineages, in the sclerotome, and subsequently within mesenchymal precursors of the axial and appendicular skeleton, before chondrogenesis occurs [3].
• Using the whole cell configuration of the patch clamp technique, we show that ectopic expression of I-mfa in CHO-K1 cells reduces native store-activated Ca2+ currents, whereas knock-down of endogenous I-mfa in A431 cells by RNA interference enhances these currents [4].

Anatomical context of Mdfi

• Overexpression of I-mfa in rat trophoblast (Rcho-1) stem cells induced differentiation into trophoblast giant cells [3].
• When Zic1-3 and I-mfa proteins were co-expressed in cultured cells, nuclear import of the Zic proteins was inhibited [5].
• The aim of this study was to examine the expression and regulation of I-mfa in osteoblasts [6].
• I-mfa expression was also observed in primary mouse calvaria cells and ROS17/2.8 cells and 1,25-dihydroxyvitamin D(3) enhanced I-mfa expression in these cells [6].
• We found that I-mfa is expressed at a low level in an osteoblast-like cell line, MC3T3E1, and a pluripotent differentiation modulator, 1,25-dihydroxyvitamin D(3), specifically enhanced I-mfa mRNA expression [6].

Physical interactions of Mdfi

• I-mf can also interfere with the DNA binding activity of MyoD family members [2].
• We found that beta-catenin interacted with I-mfa and that the interaction was enhanced by Wnt3a [7].

Regulatory relationships of Mdfi

• Beta-catenin regulates myogenesis by relieving I-mfa-mediated suppression of myogenic regulatory factors in P19 cells [7].
• Consequently, I-mfa inhibited transcriptional activation by the Zic proteins in cultured cells [5].

Other interactions of Mdfi

• A search for proteins binding to the amino terminal domain of Zic2 revealed that inhibitor of MyoD family (I-mfa) protein, which has been identified as a repressor of myogenic helix-loop-helix class transcription factors, can physically interact with the amino terminal domain [5].

Analytical, diagnostic and therapeutic context of Mdfi

• Pipette perfusion of purified recombinant I-mfa rescues the effect of I-mfa knock-down on store-operated conductance [4].
• Western blot analysis indicated that 1,25-dihydroxyvitamin D(3) increased the I-mfa protein levels severalfold in MC3T3E1 cells [6].

References