Integrating analog and digital modes of gene expression at Arabidopsis FLC.
Integrating analog and digital modes of gene expression at Arabidopsis FLC.
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DOI：
10.7554/elife.79743
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发表时间：
2023-07-19
期刊：
影响因子：
7.7
通讯作者：
Howard M
中科院分区：
文献类型：
--
作者：
Antoniou-Kourounioti RL;Meschichi A;Reeck S;Berry S;Menon G;Zhao Y;Fozard J;Holmes T;Zhao L;Wang H;Hartley M;Dean C;Rosa S;Howard M
在细胞群体水平上的定量基因调控可以通过在单个基因拷贝上的两种根本不同的调控模式来实现。"数字“模式涉及二进制ON/OFF表达状态，其中群体水平变化由每个状态中基因拷贝的比例引起，而”模拟“模式涉及每个基因拷贝的分级表达水平。在拟南芥花抑制基因FLOWARDINLOCUS C（FLC）中，“数字”Polycomb沉默被认为有助于对冷的定量表观遗传记忆。然而，FLC调节在冷之前是否涉及模拟或数字模式是未知的。利用FLC mRNA和蛋白质的定量荧光成像，结合数学建模，我们发现，FLC表达在冷之前是由模拟和数字模式调节的。我们观察到两种模式之间的时间分离，模拟在数字之前。在随后的数字沉默之前，类似模式可以在个体FLC基因拷贝处维持中间表达水平，这与拷贝在没有寒冷的情况下随机地和遗传地关闭一致。这种转换导致FLC表达在细胞群体水平上缓慢降低。这些数据提出了一个新的模式，逐步镇压，阐明模拟转录和数字表观遗传记忆通路可以整合。
Quantitative gene regulation at the cell population level can be achieved by two fundamentally different modes of regulation at individual gene copies. A ‘digital’ mode involves binary ON/OFF expression states, with population-level variation arising from the proportion of gene copies in each state, while an ‘analog’ mode involves graded expression levels at each gene copy. At the Arabidopsis floral repressor FLOWERING LOCUS C (FLC), ‘digital’ Polycomb silencing is known to facilitate quantitative epigenetic memory in response to cold. However, whether FLC regulation before cold involves analog or digital modes is unknown. Using quantitative fluorescent imaging of FLC mRNA and protein, together with mathematical modeling, we find that FLC expression before cold is regulated by both analog and digital modes. We observe a temporal separation between the two modes, with analog preceding digital. The analog mode can maintain intermediate expression levels at individual FLC gene copies, before subsequent digital silencing, consistent with the copies switching OFF stochastically and heritably without cold. This switch leads to a slow reduction in FLC expression at the cell population level. These data present a new paradigm for gradual repression, elucidating how analog transcriptional and digital epigenetic memory pathways can be integrated.