COMBINATORIAL REGULATION OF MUSCLE TRANSCRIPTION

描述(逐字摘自调查人员摘要)：长期 这些研究的目标是确定控制基因转录的程序 骨骼肌、心肌和平滑肌的测定和鉴别。 启动或抑制肌肉细胞生长和分化的努力 损伤、疾病或由于先天畸形而需要更大的 了解这些血统中的基本遗传控制。这个 肌肉特异性基因调控转录因子的鉴定 表达和定义这些调节因子如何发挥作用至关重要 了解体内肌肉发生的控制机制。假设 这些研究表明，肌肉发生的转录调控是由 多组转录因子，它们的功能组合在一起驱动 在每个不同肌肉中独特的时空模式的基因表达 血统。例如，肌细胞增强因子2的转录因子 (MEF2)和MyoD家族是相互之间和功能所必需的辅助因子 联合用来诱导骨骼肌成肌。有证据表明 MEF2蛋白也具有组合功能，可诱导分化 心肌和平滑肌。然而，到目前为止，还没有“MyoD等价物”作为 MEF2的协同调节因子已经从其他肌肉系中分离出来。这个 本申请中提出的研究旨在识别转录 心肌和平滑肌中的调节剂，在这方面与MyoD相当 它们通过组合相互作用诱导肌肉发生和基因表达 有MEF2因子。这项建议的具体目的是：1)界定 对HRC的转录调控，这是一种在所有三种细胞中都表达的基因 哺乳动物发育过程中和成体的肌肉谱系。初步数据 提示MEF2因子与先前未知的DNA结合协同作用 在心肌和平滑肌细胞中直接表达HRC的蛋白质。2) 目的：确定在平滑肌和心肌中与MyoD类似的MEF2协调控子。

DESCRIPTION (appended verbatim from investigator's abstract): The long term goal of these studies is to define the transcriptional programs controlling the determination and differentiation of skeletal, cardiac, and smooth muscle. Efforts to initiate or inhibit muscle cell growth and differentiation following injury, disease, or as a result of congenital abnormalities require a greater understanding of basic genetic control within these lineages. The identification of the transcription factors regulating muscle specific gene expression and defining how these regulators function is critical to understanding the mechanisms controlling myogenesis in vivo. The hypothesis for these studies is that transcriptional regulation of myogenesis is controlled by multiple sets of transcription factors which function combinatorially to drive gene expression in a unique temporospatial pattern within each distinct muscle lineage. For example, transcription factors of the myocyte enhancer factor 2 (MEF2) and MyoD families are essential cofactors for one another and function combinatorially to induce myogenesis in skeletal muscle. Evidence suggests that MEF2 proteins also function combinatorially to induce differentiation of cardiac and smooth muscle. However, to date no "MyoD equivalents" serving as coregulators for MEF2 have been isolated from other muscle lineages. The studies proposed in this application are designed to identify transcriptional regulators in cardiac and smooth muscle that are comparable to MyoD in that they induce myogenesis and gene expression through combinatorial interactions with MEF2 factors. The specific aims of this proposal are: 1) To define the transcriptional regulation of HRC, a gene which is expressed in all three muscle lineages in mammals during development and in adults. Preliminary data suggests that MEF2 factors collaborate with previously unidentified DNA binding proteins to direct expression of HRC in cardiac and smooth muscle lineages. 2) To identify MEF2 coregulators comparable to MyoD in smooth and cardiac muscle.