Scalable control of developmental timetables by epigenetic switching networks.
Scalable control of developmental timetables by epigenetic switching networks.
复制标题
通过表观遗传开关网络对发育时间表进行可扩展的控制。
DOI：
10.1098/rsif.2021.0109
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Kueh,HaoYuan
中科院分区：
文献类型：
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作者：
Nguyen,Phuc;Pease,NicholasA;Kueh,HaoYuan
在发育过程中，祖细胞遵循跨越许多细胞代的分化时间表。这些发育时间表由胚胎严格编码，但可以通过进化进行大规模调整，促进生物体大小和形态的变化。表观遗传开关涉及调控基因位点的限速激活步骤，控制不同背景下的基因激活时间，并可能深刻影响控制发育谱系规范的基因调控网络的动态。在这里，我们开发了一个数学框架来模拟由表观遗传开关控制的基因的调控网络。使用这个框架，我们表明，这种表观遗传转换网络支持稳健地跨越许多细胞世代的发育时间表，并能够以精确定义的数量和分数生成分化细胞。表观遗传转换网络的变化可以很容易地改变时间表内发育事件的时间安排，或者改变时间表展开的总体速度，从而能够对差异化的种群规模进行可扩展的控制。凭借其强大且灵活可调的性质，表观遗传转换网络可以代表进化作用以制造生物体大小和形态多样性的中心目标。
During development, progenitor cells follow timetables for differentiation that span many cell generations. These developmental timetables are robustly encoded by the embryo, yet scalably adjustable by evolution, facilitating variation in organism size and form. Epigenetic switches, involving rate-limiting activation steps at regulatory gene loci, control gene activation timing in diverse contexts, and could profoundly impact the dynamics of gene regulatory networks controlling developmental lineage specification. Here, we develop a mathematical framework to model regulatory networks with genes controlled by epigenetic switches. Using this framework, we show that such epigenetic switching networks uphold developmental timetables that robustly span many cell generations, and enable the generation of differentiated cells in precisely defined numbers and fractions. Changes to epigenetic switching networks can readily alter the timing of developmental events within a timetable, or alter the overall speed at which timetables unfold, enabling scalable control over differentiated population sizes. With their robust, yet flexibly adjustable nature, epigenetic switching networks could represent central targets on which evolution acts to manufacture diversity in organism size and form.