Myocyte enhancer factor 2c (MEF2C) is the MADS-box type transcription factor involved in the differentiation of cardiac and skeletal muscle and synaptic formation. Alternatively spliced transcripts of the MEF2C gene were proven to encode isoforms which exert distinct functions in transcriptional regulation. During the differentiation of brown adipocytes, upregulated RBM4 enhanced skipping of the MEF2Cγ region which functions as a transcriptional repressor. The presence of an overexpressed MEF2Cγ- isoform in turn induced transcriptional activity of the RBM4 promoter, constituting a positive feedback circuit in differentiating brown adipocytes. The RBM4-MEF2Cγ- network induced the expression of "myogenic" miR-1 to a greater extent than did PRDM17, BMP7 C/EBPβ, or UCP1 transcripts in C3H10T1/2 cells. Overexpression of miR-1 independently exerted the same activity as RBM4 and the MEF2Cγ- isoform of upregulating brown adipocyte-specific factors in C3H10T1/2 cells, which suggests a potential effect of miR-1 on brown adipocytes. These results indicated that the RBM4-MEF2C-miR-1 network constitutes a novel mechanism which programs the gene expression profile toward the development of brown adipocytes.
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机译：心肌细胞增强因子2c（MEF2C）是MADS-box型转录因子，参与心肌和骨骼肌的分化以及突触形成。事实证明，MEF2C基因的剪接转录本可编码在转录调控中发挥独特功能的同工型。在褐色脂肪细胞的分化过程中，RBM4的上调增强了MEF2Cγ区域的跳跃，该区域起着转录抑制因子的作用。过表达的MEF2Cγ-同工型的存在反过来又诱导了RBM4启动子的转录活性，在分化的棕色脂肪细胞中构成了正反馈回路。与PRDM17，BMP7 C /EBPβ或UCP1转录本在C3H10T1 / 2细胞中相比，RBM4-MEF2Cγ-网络诱导“成肌” miR-1的表达程度更高。 miR-1的过表达独立发挥与RBM4相同的活性，并在C3H10T1 / 2细胞中上调褐色脂肪细胞特异性因子的MEF2Cγ-同工型，这表明miR-1对褐色脂肪细胞的潜在作用。这些结果表明，RBM4-MEF2C-miR-1网络构成了一种新的机制，该机制将基因表达谱编程为褐色脂肪细胞的发育。
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