调解人
RNA聚合酶Ⅱ
增强子
转录前起始复合物
转录因子ⅡE
染色质
转录因子II F
增强子rna
抄写(语言学)
细胞生物学
生物
发起人
一般转录因子
真核转录
遗传学
转录调控
转录因子
计算生物学
化学
基因
基因表达
哲学
语言学
作者
William F. Richter,Shraddha Nayak,Janet Iwasa,Dylan J. Taatjes
标识
DOI:10.1038/s41580-022-00498-3
摘要
The Mediator complex, which in humans is 1.4 MDa in size and includes 26 subunits, controls many aspects of RNA polymerase II (Pol II) function. Apart from its size, a defining feature of Mediator is its intrinsic disorder and conformational flexibility, which contributes to its ability to undergo phase separation and to interact with a myriad of regulatory factors. In this Review, we discuss Mediator structure and function, with emphasis on recent cryogenic electron microscopy data of the 4.0-MDa transcription preinitiation complex. We further discuss how Mediator and sequence-specific DNA-binding transcription factors enable enhancer-dependent regulation of Pol II function at distal gene promoters, through the formation of molecular condensates (or transcription hubs) and chromatin loops. Mediator regulation of Pol II reinitiation is also discussed, in the context of transcription bursting. We propose a working model for Mediator function that combines experimental results and theoretical considerations related to enhancer-promoter interactions, which reconciles contradictory data regarding whether enhancer-promoter communication is direct or indirect. We conclude with a discussion of Mediator's potential as a therapeutic target and of future research directions.
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