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Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening

机译:先锋和非先锋因素的合作推动了谱系特异性染色质的开放

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摘要

Pioneer transcription factors are characterized by having the unique property of enabling the opening of closed chromatin sites, for implementation of cell fates. We previously found that the pioneer Pax7 specifies melanotrope cells through deployment of an enhancer repertoire, which allows binding of Tpit, a nonpioneer factor that determines the related lineages of melanotropes and corticotropes. Here, we investigate the relation between these two factors in the pioneer mechanism. Cell-specific gene expression and chromatin landscapes are defined by scRNAseq and chromatin accessibility profiling. We find that in vivo deployment of the melanotrope enhancer repertoire and chromatin opening requires both Pax7 and Tpit. In cells, binding of heterochromatin targets by Pax7 is independent of Tpit but Pax7-dependent chromatin opening requires Tpit. The present work shows that pioneer core properties are limited to the ability to recognize heterochromatin targets and facilitate nonpioneer binding. Chromatin opening per se may be provided through cooperation with nonpioneer factors.
机译:先锋转录因子的特征是具有独特的特性,能够实现封闭的染色质位点的开放,从而实现细胞命运。我们先前发现,先驱者Pax7通过部署增强子库来指定黑素细胞,该增强剂库允许Tpit结合,Tpit是一种非先驱因子,可决定黑素细胞和促肾上腺皮质激素的相关谱系。在这里,我们研究了先锋机制中这两个因素之间的关系。细胞特异性基因表达和染色质分布由scRNAseq和染色质可及性分析来定义。我们发现黑素体增强子库和染色质开放的体内部署需要Pax7和Tpit。在细胞中,Pax7与异染色质靶标的结合不依赖于Tpit,但是Pax7依赖的染色质开放需要Tpit。目前的工作表明,先驱者的核心特性仅限于识别异染色质靶标并促进非先驱者结合的能力。染色质本身可以通过与非先驱因素合作来提供。

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