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An Epigenetic Priming Mechanism Mediated by Nutrient Sensing Regulates Transcriptional Output during C. elegans Development
Current Biology ( IF 8.1 ) Pub Date : 2020-12-22 , DOI: 10.1016/j.cub.2020.11.060
Natalia Stec 1 , Katja Doerfel 1 , Kelly Hills-Muckey 1 , Victoria M Ettorre 2 , Sevinc Ercan 2 , Wolfgang Keil 3 , Christopher M Hammell 1
Affiliation  

Although precise tuning of gene expression levels is critical for most developmental pathways, the mechanisms by which the transcriptional output of dosage-sensitive molecules is established or modulated by the environment remain poorly understood. Here, we provide a mechanistic framework for how the conserved transcription factor BLMP-1/Blimp1 operates as a pioneer factor to decompact chromatin near its target loci during embryogenesis (hours prior to major transcriptional activation) and, by doing so, regulates both the duration and amplitude of subsequent target gene transcription during post-embryonic development. This priming mechanism is genetically separable from the mechanisms that establish the timing of transcriptional induction and functions to canalize aspects of cell-fate specification, animal size regulation, and molting. A key feature of the BLMP-1-dependent transcriptional priming mechanism is that chromatin decompaction is initially established during embryogenesis and maintained throughout larval development by nutrient sensing. This anticipatory mechanism integrates transcriptional output with environmental conditions and is essential for resuming normal temporal patterning after animals exit nutrient-mediated developmental arrests.



中文翻译:

由营养感应介导的表观遗传启动机制在秀丽隐杆线虫发育过程中调节转录输出

尽管基因表达水平的精确调节对于大多数发育途径至关重要,但对剂量敏感分子的转录输出建立或受环境调节的机制仍然知之甚少。在这里,我们提供了一个机制框架,说明保守的转录因子 BLMP-1/Blimp1 如何作为先驱因子发挥作用,在胚胎发生过程中(主要转录激活前的几个小时)分解其靶位点附近的染色质,并通过这样做来调节持续时间胚胎后发育过程中后续靶基因转录的幅度和幅度。这种启动机制在基因上与建立转录诱导时间和功能以引导细胞命运规范、动物大小调节和蜕皮等方面的机制是可分离的。BLMP-1 依赖的转录启动机制的一个关键特征是染色质分解最初是在胚胎发生过程中建立的,并通过营养感应在整个幼虫发育过程中维持。这种预期机制将转录输出与环境条件相结合,对于在动物退出营养介导的发育停滞后恢复正常的时间模式至关重要。

更新日期:2021-02-22
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