Pipes G C Teg, Creemers Esther E, Olson Eric N
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Genes Dev. 2006 Jun 15;20(12):1545-56. doi: 10.1101/gad.1428006.
The association of transcriptional coactivators with sequence-specific DNA-binding proteins provides versatility and specificity to gene regulation and expands the regulatory potential of individual cis-regulatory DNA sequences. Members of the myocardin family of coactivators activate genes involved in cell proliferation, migration, and myogenesis by associating with serum response factor (SRF). The partnership of myocardin family members and SRF also controls genes encoding components of the actin cytoskeleton and confers responsiveness to extracellular growth signals and intracellular changes in the cytoskeleton, thereby creating a transcriptional-cytoskeletal regulatory circuit. These functions are reflected in defects in smooth muscle differentiation and function in mice with mutations in myocardin family members. This article reviews the functions and mechanisms of action of the myocardin family of coactivators and the physiological significance of transcriptional coactivation in the context of signal-dependent and cell-type-specific gene regulation.
转录共激活因子与序列特异性DNA结合蛋白的结合为基因调控提供了多样性和特异性,并扩展了单个顺式调控DNA序列的调控潜力。共激活因子心肌素家族的成员通过与血清反应因子(SRF)结合来激活参与细胞增殖、迁移和肌生成的基因。心肌素家族成员与SRF的协同作用还控制着编码肌动蛋白细胞骨架成分的基因,并赋予细胞对细胞外生长信号和细胞骨架内细胞变化的反应能力,从而形成一个转录-细胞骨架调控回路。这些功能在心肌素家族成员发生突变的小鼠的平滑肌分化和功能缺陷中得到体现。本文综述了共激活因子心肌素家族的功能和作用机制,以及在信号依赖和细胞类型特异性基因调控背景下转录共激活的生理意义。