An Epigenetic Priming Mechanism Mediated by Nutrient Sensing Regulates Transcriptional Output during C. elegans Development.
An Epigenetic Priming Mechanism Mediated by Nutrient Sensing Regulates Transcriptional Output during C. elegans Development.
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DOI：
10.1016/j.cub.2020.11.060
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发表时间：
2021-02-22
期刊：
影响因子：
--
通讯作者：
Hammell CM
中科院分区：
文献类型：
--
作者：
Stec N;Doerfel K;Hills-Muckey K;Ettorre VM;Ercan S;Keil W;Hammell CM
虽然基因表达水平的精确调节对于大多数发育途径至关重要，但剂量敏感分子的转录输出由环境建立或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，保守的转录因子BLMP-1/Blimp 1如何作为一个先锋因子，在胚胎发生过程中（主要转录激活前数小时），去分解其靶位点附近的染色质，并通过这样做，调节胚胎后发育过程中后续靶基因转录的持续时间和幅度。这种启动机制是遗传分离的机制，建立转录诱导的时机和功能，以疏导方面的细胞命运的规范，动物的大小调节，和蜕皮。BLMP-1依赖的转录引发机制的一个关键特征是，染色质解压缩最初在胚胎发生期间建立，并通过营养传感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。Stec等人描述了一种新的基因机制，其中高度保守的转录因子BLMP-1通过在转录激活前数小时在特定基因座处解压缩染色质来引发其靶基因。这种机制调节许多关键基因的转录输出，这些基因在胚胎后发育过程中控制细胞命运的规范。
While 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. Stec et al. describe a novel gene mechanism where BLMP-1, a highly conserved transcription factor, primes its target genes by decompacting chromatin at specific loci hours prior to transcriptional activation. This mechanism regulates the transcriptional output of many key genes that control cell fate specification during post-embryonic development.
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