SWI/SNF chromatin remodeling ATPase Brm regulates the differentiation of early retinal stem cells/progenitors by influencing Brn3b expression and notch signaling
SWI/SNF chromatin remodeling ATPase Brm regulates the differentiation of early retinal stem cells/progenitors by influencing Brn3b expression and notch signaling
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DOI：
10.1074/jbc.m706742200
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发表时间：
2007-11-30
影响因子：
4.8
通讯作者：
Ahmad, Iqbal
中科院分区：
文献类型：
--
作者：
Das, Ani V.;James, Jackson;Ahmad, Iqbal
基于多种方法，有证据表明，脊椎动物视网膜中的不同细胞类型是由多能祖细胞响应细胞内在因素和细胞外在因素之间的相互作用而产生的。介导这种相互作用的一些细胞决定因素的身份已经出现，揭示了细胞分化的机制。例如，我们现在知道Notch信号通过激活转录阻遏物来介导微环境对祖细胞承诺状态的影响。细胞内在因子，例如原神经基本螺旋-环-螺旋和同源域转录因子，调节细胞分化和成熟所需的基因网络。这张图片中缺少的是发育染色质重塑在协调视网膜祖细胞分化的不同类别基因的表达中的作用。在这里，我们描述了 Brm（SWI/SNF 染色质重塑复合物中的一种 ATP 酶）在视网膜祖细胞分化为视网膜神经节细胞中的作用。通过表达扰动和功能分析，我们证明 Brm 通过促进视网膜神经节细胞关键调节因子 Brn3b 的表达和功能以及抑制 Notch 信号传导来促进视网膜神经节细胞分化。此外，我们证明 Brm 促进视网膜神经节细胞分化过程中的细胞周期退出。总之，我们的结果表明，Brm 代表了细胞分化过程中整合细胞分化的各种信息的联系之一。
Based on a variety of approaches, evidence suggests that different cell types in the vertebrate retina are generated by multipotential progenitors in response to interactions between cell intrinsic and cell extrinsic factors. The identity of some of the cellular determinants that mediate such interactions has emerged, shedding light on mechanisms underlying cell differentiation. For example, we know now that Notch signaling mediates the influence of the microenvironment on states of commitment of the progenitors by activating transcriptional repressors. Cell intrinsic factors such as the proneural basic helix-loop-helix and homeodomain transcription factors regulate a network of genes necessary for cell differentiation and maturation. What is missing from this picture is the role of developmental chromatin remodeling in coordinating the expression of disparate classes of genes for the differentiation of retinal progenitors. Here we describe the role of Brm, an ATPase in the SWI/SNF chromatin remodeling complex, in the differentiation of retinal progenitors into retinal ganglion cells. Using the perturbation of expression and function analyses, we demonstrate that Brm promotes retinal ganglion cell differentiation by facilitating the expression and function of a key regulator of retinal ganglion cells, Brn3b, and the inhibition of Notch signaling. In addition, we demonstrate that Brm promotes cell cycle exit during retinal ganglion cell differentiation. Together, our results suggest that Brm represents one of the nexus where diverse information of cell differentiation is integrated during cell differentiation.