Molkentin J D, Firulli A B, Black B L, Martin J F, Hustad C M, Copeland N, Jenkins N, Lyons G, Olson E N
Hamon Center for Basic Cancer Research, The University of Texas Southwestern Medical Center at Dallas, 75235-9148, YSA.
Mol Cell Biol. 1996 Jul;16(7):3814-24. doi: 10.1128/MCB.16.7.3814.
There are four members of the myocyte enhancer binding factor 2 (MEF2) family of transcription factors, MEF2A, -B, -C, and -D, that have homology within an amino-terminal MADS box and an adjacent MEF2 domain that together mediate dimerization and DNA binding. MEF2A, -C, and -D have previously been shown to bind an A/T-rich DNA sequence in the control regions of numerous muscle-specific genes, whereas MEF2B was reported to be unable to bind this sequence unless the carboxyl terminus was deleted. To further define the functions of MEF2B, we analyzed its DNA binding and transcriptional activities. In contrast to previous studies, our results show that MEF2B binds the same DNA sequence as other members of the MEF2 family and acts as a strong transactivator through that sequence. Transcriptional activation by MEF2B is dependent on the carboxyl terminus, which contains two conserved sequence motifs found in all vertebrate MEF2 factors. During mouse embryogenesis, MEF2B transcripts are expressed in the developing cardiac and skeletal muscle lineages in a temporospatial pattern distinct from but overlapping with those of the other Mef2 genes. The mouse Mef2b gene maps to chromosome 8 and is unlinked to other Mef2 genes; its intron-exon organization is similar to that of the other vertebrate Mef2 genes and the single Drosophila Mef2 gene, consistent with the notion that these different Mef2 genes evolved from a common ancestral gene.
肌细胞增强因子结合因子2(MEF2)家族有四个转录因子成员,即MEF2A、-B、-C和-D,它们在氨基末端的MADS盒和相邻的MEF2结构域内具有同源性,这两个结构域共同介导二聚化和DNA结合。先前已证明MEF2A、-C和-D能结合众多肌肉特异性基因控制区域中富含A/T的DNA序列,而据报道MEF2B无法结合该序列,除非其羧基末端被删除。为进一步确定MEF2B的功能,我们分析了其DNA结合和转录活性。与先前的研究不同,我们的结果表明MEF2B与MEF2家族的其他成员结合相同的DNA序列,并通过该序列作为强转录激活因子发挥作用。MEF2B的转录激活依赖于羧基末端,该末端包含在所有脊椎动物MEF2因子中发现的两个保守序列基序。在小鼠胚胎发育过程中,MEF2B转录本在发育中的心脏和骨骼肌谱系中以与其他Mef2基因不同但重叠的时空模式表达。小鼠Mef2b基因定位于8号染色体,与其他Mef2基因不连锁;其内含子-外显子组织与其他脊椎动物Mef2基因和单个果蝇Mef2基因相似,这与这些不同的Mef2基因从一个共同的祖先基因进化而来的观点一致。