Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Center for Genomics and Systems Biology, New York University, 100 Washington Square East, 852 Brown, New York, NY 10003, USA.
Curr Biol. 2021 Feb 22;31(4):809-826.e6. doi: 10.1016/j.cub.2020.11.060. Epub 2020 Dec 22.
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.
虽然精确调节基因表达水平对于大多数发育途径至关重要,但环境如何建立或调节剂量敏感分子的转录输出的机制仍知之甚少。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 如何作为先驱因子在胚胎发生过程中(在主要转录激活之前的几个小时)解压缩其靶基因附近的染色质,从而调节胚胎发生后发育过程中随后靶基因转录的持续时间和幅度。这种启动机制在遗传上与确定转录诱导时间的机制是可分离的,并且可以对细胞命运特化、动物大小调节和蜕皮的某些方面进行规范。BLMP-1 依赖性转录启动机制的一个关键特征是,在胚胎发生过程中最初建立染色质解压缩,并通过营养感应在幼虫发育过程中维持。这种前瞻性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。