From the Laboratory of Molecular Genetics, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Quebec H2W 1R7, Canada.
From the Laboratory of Molecular Genetics, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Quebec H2W 1R7, Canada
J Biol Chem. 2018 Sep 7;293(36):13795-13804. doi: 10.1074/jbc.R117.001232. Epub 2018 Mar 5.
Pioneer transcription factors have the unique and important role of unmasking chromatin domains during development to allow the implementation of new cellular programs. Compared with those of other transcription factors, this activity implies that pioneer factors can recognize their target DNA sequences in so-called compacted or "closed" heterochromatin and can trigger remodeling of the adjoining chromatin landscape to provide accessibility to nonpioneer transcription factors. Recent studies identified several steps of pioneer action, namely rapid but weak initial binding to heterochromatin and stabilization of binding followed by chromatin opening and loss of cytosine-phosphate-guanine (CpG) methylation that provides epigenetic memory. Whereas CpG demethylation depends on replication, chromatin opening does not. In this Minireview, we highlight the unique properties of this transcription factor class and the challenges of understanding their mechanism of action.
先驱转录因子在发育过程中具有揭示染色质结构域的独特而重要的作用，以允许新的细胞程序的实施。与其他转录因子相比，这种活性意味着先驱因子可以在所谓的致密或“封闭”异染色质中识别其靶 DNA 序列，并可以触发相邻染色质结构域的重塑，以提供非先驱转录因子的可及性。最近的研究确定了先驱作用的几个步骤，即快速但弱的初始与异染色质结合，以及随后的结合稳定，接着是染色质开放和胞嘧啶-磷酸-鸟嘌呤（CpG）甲基化的丢失，提供了表观遗传记忆。虽然 CpG 去甲基化依赖于复制，但染色质开放则不然。在这篇综述中，我们强调了这种转录因子类的独特性质及其作用机制理解所面临的挑战。
