Scales J B, Olson E N, Perry M
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Mol Cell Biol. 1990 Apr;10(4):1516-24. doi: 10.1128/mcb.10.4.1516-1524.1990.
The myogenic factors MyoD1 and myogenin contain a conserved region with similarity to the myc family of proto-oncogenes. To identify amphibian genes structurally and functionally related to these myogenic factors, we screened a Xenopus laevis embryo cDNA library under conditions of reduced stringency with probes corresponding to the myc-like helix-loop-helix motif of mouse MyoD1 and myogenin. Several distinct cDNAs that are highly related to each other and share extensive homology to MyoD1 were isolated. Transcripts from two of these genes, Xlmf1 and Xlmf25 (X. laevis myogenic factor), reach maximal levels of accumulation during gastrulation, remain at constant levels through early embryogenesis, and are found exclusively in skeletal muscles of adult frogs. The appearance of these transcripts early in development precedes the expression of cardiac alpha-actin, a molecular marker for mesoderm formation. A third cDNA, Xlmf11, contains an internal 351-base-pair deletion downstream of the myc homology region and encodes a truncated version of the protein encoded by Xlmf1. When expressed in mouse pluripotential stem cells, Xlmf1 activates the muscle cell differentiation program, resulting in expression of endogenous MyoD1, myogenin, and myosin heavy-chain genes and formation of multinucleated myotubes.
生肌因子MyoD1和肌细胞生成素含有一个与原癌基因myc家族相似的保守区域。为了鉴定在结构和功能上与这些生肌因子相关的两栖类基因，我们用对应于小鼠MyoD1和肌细胞生成素的类myc螺旋-环-螺旋基序的探针，在低严谨条件下筛选非洲爪蟾胚胎cDNA文库。分离出了几个彼此高度相关且与MyoD1有广泛同源性的不同cDNA。其中两个基因Xlmf1和Xlmf25（非洲爪蟾生肌因子）的转录本在原肠胚形成期间积累达到最高水平，在早期胚胎发育过程中保持恒定水平，并且仅在成年青蛙的骨骼肌中发现。这些转录本在发育早期的出现先于中胚层形成的分子标记——心肌α-肌动蛋白的表达。第三个cDNA Xlmf11在myc同源区域下游含有一个351个碱基对的内部缺失，并编码由Xlmf1编码的蛋白质的截短版本。当在小鼠多能干细胞中表达时，Xlmf1激活肌肉细胞分化程序，导致内源性MyoD1、肌细胞生成素和肌球蛋白重链基因的表达以及多核肌管的形成。
