Single-stranded DNA binding proteins are required for LIM complexes to induce transcriptionally active chromatin and specify spinal neuronal identities
Single-stranded DNA binding proteins are required for LIM complexes to induce transcriptionally active chromatin and specify spinal neuronal identities
复制标题
DOI：
10.1242/dev.131284
复制
发表时间：
2016-05-15
期刊：
影响因子：
4.6
通讯作者：
Lee, Soo-Kyung
中科院分区：
文献类型：
--
作者：
Lee, Bora;Lee, Seunghee;Lee, Soo-Kyung
LIM同源结构域因子调节许多细胞类型的发育。然而，转录辅激活因子介导的发育功能仍然不清楚。为了解决这些问题，我们研究了两个相关的NLI依赖的LIM复合物，这支配脊髓运动神经元和V2 a中间神经元的发育，激活胚胎脊髓中的转录。我们发现单链DNA结合蛋白通过NLI被募集到这些LIM复合物中，并增强其转录激活潜力。Ssdp 1和Ssdp 2（Ssdp 1/2）在神经管中高度表达，并促进胚胎脊髓和P19干细胞中运动神经元的分化。在小鼠和鸡胚中抑制Ssdp 1/2活性抑制运动神经元和V2 a中间神经元的产生。此外，Ssdp 1/2招募组蛋白修饰酶到运动神经元特异性LIM复合物，并触发组蛋白H3的乙酰化和赖氨酸4三甲基化，这是公认的活性转录的染色质标记。我们的研究结果表明，Ssdp 1/2功能作为关键的转录辅激活LIM复合物，以指定脊髓神经元的身份在发展过程中。
LIM homeodomain factors regulate the development of many cell types. However, transcriptional coactivators that mediate their developmental function remain poorly defined. To address these, we examined how two related NLI-dependent LIM complexes, which govern the development of spinal motor neurons and V2a interneurons, activate the transcription in the embryonic spinal cord. We found that single-stranded DNA-binding proteins are recruited to these LIM complexes via NLI, and enhance their transcriptional activation potential. Ssdp1 and Ssdp2 (Ssdp1/2) are highly expressed in the neural tube and promote motor neuron differentiation in the embryonic spinal cord and P19 stem cells. Inhibition of Ssdp1/2 activity in mouse and chick embryos suppresses the generation of motor neurons and V2a interneurons. Furthermore, Ssdp1/2 recruit histone-modifying enzymes to the motor neuron-specifying LIM complex and trigger acetylation and lysine 4 trimethylation of histone H3, which are well-established chromatin marks for active transcription. Our results suggest that Ssdp1/2 function as crucial transcriptional coactivators for LIM complexes to specify spinal neuronal identities during development.