MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206.

MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206.
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DOI:
10.1083/jcb.200603039
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发表时间:
2006-10-09
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Tapscott SJ
Tapscott SJ
中科院分区:
其他
文献类型:
--
作者:
Rosenberg MI;Georges SA;Asawachaicharn A;Analau E;Tapscott SJ

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不同细胞类型的终末分化需要分化特异性基因的转录激活和与前体细胞相关的基因的抑制。例如,肌营养蛋白(Utrn)的表达在骨骼肌分化过程中受到抑制,并且它在肌膜处被相关的肌营养不良蛋白质取代。MyoD转录因子直接激活大量骨骼肌基因的表达,但也抑制许多基因的表达。为了表征MyoD介导的基因表达抑制机制,我们研究了MyoD转化为骨骼肌的成纤维细胞中抑制的两个基因,卵泡抑素样1(Fstl 1)和Utrn。MyoD直接激活肌肉特异性microRNA(miRNA)miR-206的表达,miR-206靶向Fstl 1和Utrn RNA中的序列,这些序列足以在miR-206存在下抑制基因表达。这些发现表明,MyoD除了激活肌肉特异性基因外,还诱导抑制骨骼肌分化过程中基因表达的miRNA。
Terminal differentiation of distinct cell types requires the transcriptional activation of differentiation-specific genes and the suppression of genes associated with the precursor cell. For example, the expression of utrophin (Utrn) is suppressed during skeletal muscle differentiation, and it is replaced at the sarcolemma by the related dystrophin protein. The MyoD transcription factor directly activates the expression of a large number of skeletal muscle genes, but also suppresses the expression of many genes. To characterize a mechanism of MyoD-mediated suppression of gene expression, we investigated two genes that are suppressed in fibroblasts converted to skeletal muscle by MyoD, follistatin-like 1 (Fstl1) and Utrn. MyoD directly activates the expression of a muscle-specific microRNA (miRNA), miR-206, which targets sequences in the Fstl1 and Utrn RNA, and these sequences are sufficient to suppress gene expression in the presence of miR-206. These findings demonstrate that MyoD, in addition to activating muscle-specific genes, induces miRNAs that repress gene expression during skeletal muscle differentiation.
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