Gajewski K, Kim Y, Lee Y M, Olson E N, Schulz R A
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
EMBO J. 1997 Feb 3;16(3):515-22. doi: 10.1093/emboj/16.3.515.
The NK-type homeobox gene tinman and the MADS box gene D-mef2 encode transcription factors required for the development and differentiation of the Drosophila heart, and closely related genes regulate cardiogenesis in vertebrates. Genetic analyses indicate that tinman and D-mef2 act at early and late steps, respectively, in the cardiogenic lineage. However, it is unknown whether regulatory interactions exist between these developmental control genes. We show that D-mef2 expression in the developing Drosophila heart requires a novel upstream enhancer containing two Tinman binding sites, both of which are essential for enhancer function in cardiac muscle cells. Transcriptional activity of this cardiac enhancer is dependent on tinman function, and ectopic Tinman expression activates the enhancer outside the cardiac lineage. These results define the only known in vivo target for transcriptional activation by Tinman and demonstrate that D-mef2 lies directly downstream of tinman in the genetic cascade controlling heart formation in Drosophila.
NK 型同源盒基因tinman和MADS 盒基因D-mef2编码果蝇心脏发育和分化所需的转录因子，并且与之密切相关的基因调控脊椎动物的心脏发生。遗传分析表明，tinman和D-mef2分别在心脏发生谱系的早期和晚期发挥作用。然而，这些发育控制基因之间是否存在调控相互作用尚不清楚。我们发现，发育中的果蝇心脏中D-mef2的表达需要一个新的上游增强子，该增强子包含两个Tinman结合位点，这两个位点对于心肌细胞中的增强子功能都是必不可少的。这个心脏增强子的转录活性依赖于tinman的功能，异位的Tinman表达会在心脏谱系之外激活该增强子。这些结果确定了Tinman转录激活的唯一已知体内靶点，并证明在控制果蝇心脏形成的遗传级联反应中，D-mef2直接位于tinman的下游。
