Cis-regulatory control of transcriptional timing and noise in response to estrogen.

IF 11.1 Q1 CELL BIOLOGY
Cell genomics Pub Date : 2024-05-08 Epub Date: 2024-04-24 DOI:10.1016/j.xgen.2024.100542
Matthew Ginley-Hidinger, Hosiana Abewe, Kyle Osborne, Alexandra Richey, Noel Kitchen, Katelyn L Mortenson, Erin M Wissink, John Lis, Xiaoyang Zhang, Jason Gertz
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引用次数: 0

Abstract

Cis-regulatory elements control transcription levels, temporal dynamics, and cell-cell variation or transcriptional noise. However, the combination of regulatory features that control these different attributes is not fully understood. Here, we used single-cell RNA-seq during an estrogen treatment time course and machine learning to identify predictors of expression timing and noise. We found that genes with multiple active enhancers exhibit faster temporal responses. We verified this finding by showing that manipulation of enhancer activity changes the temporal response of estrogen target genes. Analysis of transcriptional noise uncovered a relationship between promoter and enhancer activity, with active promoters associated with low noise and active enhancers linked to high noise. Finally, we observed that co-expression across single cells is an emergent property associated with chromatin looping, timing, and noise. Overall, our results indicate a fundamental tradeoff between a gene's ability to quickly respond to incoming signals and maintain low variation across cells.

顺式调节控制转录时间和噪音对雌激素的反应
顺式调控元件控制着转录水平、时间动态、细胞间差异或转录噪音。然而,控制这些不同属性的调控特征的组合还不完全清楚。在这里,我们利用雌激素治疗时间过程中的单细胞 RNA-seq和机器学习来识别表达时间和噪音的预测因子。我们发现,具有多个活跃增强子的基因表现出更快的时间反应。我们通过研究发现,增强子的活性会改变雌激素靶基因的时间反应,从而验证了这一发现。对转录噪音的分析发现了启动子和增强子活性之间的关系,活跃的启动子与低噪音相关,而活跃的增强子与高噪音相关。最后,我们观察到,单细胞间的共表达是一种与染色质循环、时间和噪声相关的新兴特性。总之,我们的研究结果表明,在基因快速响应传入信号的能力与保持跨细胞低变异的能力之间存在着根本性的权衡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
7.10
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