Corl1, a novel neuronal lineage-specific transcriptional corepressor for the hameodomain transcription factor Lbx1
Corl1, a novel neuronal lineage-specific transcriptional corepressor for the hameodomain transcription factor Lbx1
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DOI：
10.1074/jbc.m411652200
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发表时间：
2005-02-04
影响因子：
4.8
通讯作者：
Ono, Y
中科院分区：
文献类型：
--
作者：
Mizuhara, E;Nakatani, T;Ono, Y
在发育过程中，神经元的身份是由许多转录因子的组合决定的。然而，这些因子在转录调控和随后的细胞命运规范中的协同作用机制在很大程度上是未知的。在这项研究中，我们发现了一个新的基因，Corl1，编码一个与Ski癌蛋白同源的核蛋白。Corl1在中枢神经系统（CNS）中高度选择性表达。在胚胎中枢神经系统中，Corl1在中脑-后脑边界后方产生的有丝分裂后神经元的特定亚群中表达。在发育中的脊髓中，Corl1选择性地在背角中间神经元中表达，在那里同源结构域转录因子Lbx1需要适当的规范。Corl1定位于核点状结构，并与一般的转录辅抑制子相互作用。此外，Corl1在gal4融合系统中表现出转录抑制活性，表明其参与了转录抑制的调控。此外，Corl1与Lbx1相互作用并协同抑制转录，这表明它作为Lbx1的转录共抑制因子调节脊髓背区细胞命运的决定。Corl1共阻遏因子活性不依赖于Gro/TLE活性，Gro/TLE也作为Lbx1的共阻遏因子。因此，Lbx1可以选择两个独立的伙伴Corl1和Gro/TLE作为协抑制因子。鉴定一种具有神经元亚型限制性表达的新型转录共抑制因子可能为神经元细胞命运决定的机制提供见解。
During development, neuronal identity is determined by a combination of numerous transcription factors. However, the mechanisms of synergistic action of these factors in transcriptional regulation and subsequent cell fate specification are largely unknown. In this study, we identified a novel gene, Corl1, encoding a nuclear protein with homology to the Ski oncoprotein. Corl1 was highly selectively expressed in the central nervous system (CNS). In the embryonic CNS, Corl1 was expressed in a certain subset of postmitotic neurons generated posterior to the midbrain-hindbrain border. In the developing spinal cord, Corl1 was selectively expressed in the dorsal horn interneurons where a homeodomain transcription factor, Lbx1, is required for proper specification. Corl1 was localized in a nuclear dot-like structure and interacted with general transcriptional corepressors. In addition, Corl1 showed transcriptional repression activity in the GAL4-fusion system, indicating its involvement in the regulation of transcriptional repression. Furthermore, Corl1 interacted with Lbx1 and cooperatively repressed transcription, suggesting that it acts as a transcriptional corepressor for Lbx1 in regulating cell fate determination in the dorsal spinal cord. Corl1 corepressor activity did not depend on Gro/TLE activity, and Gro/TLE also functioned as a corepressor for Lbx1. Thus, Lbx1 can select two independent partners, Corl1 and Gro/TLE, as corepressors. Identification of a novel transcriptional corepressor with neuronal subtype-restricted expression might provide insights into the mechanisms of cell fate determination in neurons.