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Dosage Sensing, Threshold Responses, and Epigenetic Memory: A Systems Biology Perspective on Random X-Chromosome Inactivation.
BioEssays ( IF 3.2 ) Pub Date : 2020-03-19 , DOI: 10.1002/bies.201900163 Verena Mutzel 1 , Edda G Schulz 1
BioEssays ( IF 3.2 ) Pub Date : 2020-03-19 , DOI: 10.1002/bies.201900163 Verena Mutzel 1 , Edda G Schulz 1
Affiliation
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X‐chromosome inactivation ensures dosage compensation between the sexes in mammals by randomly choosing one out of the two X chromosomes in females for inactivation. This process imposes a plethora of questions: How do cells count their X chromosome number and ensure that exactly one stays active? How do they randomly choose one of two identical X chromosomes for inactivation? And how do they stably maintain this state of monoallelic expression? Here, different regulatory concepts and their plausibility are evaluated in the context of theoretical studies that have investigated threshold behavior, ultrasensitivity, and bistability through mathematical modeling. It is discussed how a twofold difference between a single and a double dose of X‐linked genes might be converted to an all‐or‐nothing response and how mutually exclusive expression can be initiated and maintained. Finally, candidate factors that might mediate the proposed regulatory principles are reviewed.
中文翻译：
剂量感应，阈值反应和表观遗传记忆：随机X染色体失活的系统生物学观点。
X染色体失活可通过从雌性的两个X染色体中随机选择一个进行灭活来确保哺乳动物性别之间的剂量补偿。这个过程带来了很多问题：细胞如何计数其X染色体数并确保一个细胞保持活跃？他们如何随机选择两个相同的X染色体之一进行灭活？以及它们如何稳定地维持这种单等位基因表达状态？在这里，在理论研究的背景下评估了不同的监管概念及其合理性，这些理论研究已通过数学建模研究了阈值行为，超敏性和双稳态。讨论了单剂量和双剂量X连锁基因之间的两倍差异如何转换为全有或全无响应，以及如何启动和维持互斥表达。最后，对可能介导拟议监管原则的候选因素进行了审查。
更新日期：2020-03-26
中文翻译：
剂量感应，阈值反应和表观遗传记忆：随机X染色体失活的系统生物学观点。
X染色体失活可通过从雌性的两个X染色体中随机选择一个进行灭活来确保哺乳动物性别之间的剂量补偿。这个过程带来了很多问题：细胞如何计数其X染色体数并确保一个细胞保持活跃？他们如何随机选择两个相同的X染色体之一进行灭活？以及它们如何稳定地维持这种单等位基因表达状态？在这里，在理论研究的背景下评估了不同的监管概念及其合理性，这些理论研究已通过数学建模研究了阈值行为，超敏性和双稳态。讨论了单剂量和双剂量X连锁基因之间的两倍差异如何转换为全有或全无响应，以及如何启动和维持互斥表达。最后，对可能介导拟议监管原则的候选因素进行了审查。
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