CoRest1 regulates neurogenesis in a stage-dependent manner.
CoRest1 regulates neurogenesis in a stage-dependent manner.
复制标题
CoRest1 以阶段依赖性方式调节神经发生。
DOI：
10.1002/dvdy.86
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Sirotkin,HowardI
中科院分区：
文献类型：
--
作者：
Monestime,CamilliaM;Taibi,Andrew;Gates,KeithP;Jiang,Karen;Sirotkin,HowardI
背景发育过程，包括神经元分化，需要转录的精确调节。 RE-1 沉默转录因子（Rest）由于其大量的神经特异性靶标而通常被称为“主神经元调节因子”。 Rest 将 CoRest (Rcor) 和 Sin3 辅阻遏物复合物招募到基因调控序列中。 CoRest 不仅与 Rest 相关，还与其他转录调节因子相关。在这项研究中，我们使用类转录激活因子效应核酸酶 (TALENS) 生成了斑马鱼rcor1 突变体，以研究其在抑制 Rest 靶基因以及与 Rest 无关的 Rcor1 发育功能中的必要作用。结果虽然适应性略有下降，但大多数都存活下来并产生了可存活的后代。我们检查了母体 zygoticrcor1 (MZrcor1) 突变体中包含 RE1 的基因的表达水平，发现 Rcor1 通常不是早期抑制 Rest 靶基因所必需的。然而，与对照组相比，MZrcor1 突变体的神经发生速度更快。我们发现，在原肠胚阶段，Rcor1 作为hergene 家族的阻遏蛋白，但在后期阶段，MZrcor1 突变体中的her6 减少。结论基于这些发现，CoRest1 在神经发生中的核心作用可能是由于其与休息无关的作用，而不是作为休息辅阻遏物。
BackgroundDevelopmental processes, including neuronal differentiation, require precise regulation of transcription. The RE‐1 silencing transcription factor (Rest), is often called a “master neuronal regulator” due to its large number of neural‐specific targets. Rest recruits CoRest (Rcor) and Sin3 corepressor complexes to gene regulatory sequences. CoRest not only associates with Rest, but with other transcription regulators. In this study, we generated zebrafishrcor1mutants using transcription activator‐like effector nucleases (TALENS), to study its requisite role in repression of Rest target genes as well as Rest‐independent Rcor1 developmental functions.ResultsWhilercor1mutants have a slight decrease in fitness, most survived and produced viable offspring. We examined expression levels of RE1‐containing genes in maternal zygoticrcor1(MZrcor1) mutants and found that Rcor1 is generally not required for the repression of Rest target genes at early stages. However, MZrcor1mutants undergo more rapid neurogenesis compared to controls. We found that at gastrula stages, Rcor1 acts as a repressor ofhergene family, but at later stages, her6 decreased in the MZrcor1mutant.ConclusionsBased on these findings, the central role of CoRest1 in neurogenesis is likely due to a Rest‐independent role rather than as a Rest corepressor.