Transcriptional activity of MEF2 during mouse embryogenesis monitored with a MEF2-dependent transgene.
Transcriptional activity of MEF2 during mouse embryogenesis monitored with a MEF2-dependent transgene.
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发表时间：
1999-05
期刊：
影响因子：
4.6
通讯作者：
F. Naya;Chuanzhen Wu;James A. Richardson;P. Overbeek;Eric N. Olson
中科院分区：
文献类型：
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作者：
F. Naya;Chuanzhen Wu;James A. Richardson;P. Overbeek;Eric N. Olson
MADS盒转录因子MEF 2家族的四个成员MEF 2-A、MEF 2-B、MEF 2-C和MEF 2-D在胚胎发生期间以重叠模式在发育中的肌肉和神经细胞谱系中表达。然而，在胎儿发育后期和出生后，MEF 2转录本也在广泛的细胞类型中表达。由于MEF 2表达受翻译和翻译后机制控制，因此尚不清楚胚胎中MEF 2转录本的存在是否反映了转录活性的MEF 2蛋白。为了确定在小鼠胚胎发生过程中转录活性MEF 2蛋白的时空表达模式，我们产生了转基因小鼠，该小鼠携带由MEF 2位点的三个串联拷贝和来自结蛋白增强子的侧翼序列控制的lacZ报告基因，该增强子在心脏、骨骼和平滑肌细胞中具有活性。这种MEF 2依赖性转基因的表达抑制了MEF 2 mRNA在发育中的肌源性谱系和成人大脑区域中的表达。然而，它在表达MEF 2转录本的其他细胞类型中不表达。来自c-jun启动子的MEF 2位点的串联拷贝以与结蛋白MEF 2位点类似的模式指导表达，表明转基因表达反映了转录活性MEF 2蛋白的存在，而不是MEF 2位点侧翼DNA序列特异性的其他因子。这些结果表明，在胚胎发生过程中的早期肌肉和神经细胞谱系中存在转录活性MEF 2蛋白，并反对谱系限制MEF 2辅因子的存在，该辅因子区分具有不同直接侧翼序列的MEF 2位点。MEF 2 mRNA表达和MEF 2转录活性在胚胎和成人的非肌肉细胞类型之间的不一致性也支持转录后机制调节MEF 2蛋白表达的观点。
The four members of the MEF2 family of MADS-box transcription factors, MEF2-A, MEF2-B, MEF2-C and MEF2-D, are expressed in overlapping patterns in developing muscle and neural cell lineages during embryogenesis. However, during late fetal development and postnatally, MEF2 transcripts are also expressed in a wide range of cell types. Because MEF2 expression is controlled by translational and post-translational mechanisms, it has been unclear whether the presence of MEF2 transcripts in the embryo reflects transcriptionally active MEF2 proteins. To define the temporospatial expression pattern of transcriptionally active MEF2 proteins during mouse embryogenesis, we generated transgenic mice harboring a lacZ reporter gene controlled by three tandem copies of the MEF2 site and flanking sequences from the desmin enhancer, which is active in cardiac, skeletal and smooth muscle cells. Expression of this MEF2-dependent transgene paralleled expression of MEF2 mRNAs in developing myogenic lineages and regions of the adult brain. However, it was not expressed in other cell types that express MEF2 transcripts. Tandem copies of the MEF2 site from the c-jun promoter directed expression in a similar pattern to the desmin MEF2 site, suggesting that transgene expression reflects the presence of transcriptionally active MEF2 proteins, rather than other factors specific for DNA sequences flanking the MEF2 site. These results demonstrate the presence of transcriptionally active MEF2 proteins in the early muscle and neural cell lineages during embryogenesis and argue against the existence of lineage-restricted MEF2 cofactors that discriminate between MEF2 sites with different immediate flanking sequences. The discordance between MEF2 mRNA expression and MEF2 transcriptional activity in nonmuscle cell types of embryos and adults also supports the notion that post-transcriptional mechanisms regulate the expression of MEF2 proteins.