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转录爆发期间基因组区域邻近性的转录偶联变化。

Transcription-coupled changes in genomic region proximities during transcriptional bursting.

作者信息

Ohishi Hiroaki, Shinkai Soya, Owada Hitoshi, Fujii Takeru, Hosoda Kazufumi, Onami Shuichi, Yamamoto Takashi, Ohkawa Yasuyuki, Ochiai Hiroshi

机构信息

Division of Gene Expression Dynamics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.

Laboratory for Developmental Dynamics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.

出版信息

Sci Adv. 2024 Dec 6;10(49):eadn0020. doi: 10.1126/sciadv.adn0020.

Abstract

The orchestration of our genes heavily relies on coordinated communication between enhancers and promoters, yet the mechanisms behind this dynamic interplay during active transcription remain unclear. Here, we investigated enhancer-promoter (E-P) interactions in relation to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence-fluorescence in situ hybridization analyses. Our data reveal that the active state of specific genes is characterized by specific proximities between different genomic regions and the accumulation of transcriptional regulatory factors. Mathematical simulations suggest that an increase in local viscosity could potentially contribute to stabilizing the duration of these E-P proximities. Our study provides insights into the association among E-P proximity, protein accumulation, and transcriptional dynamics, paving the way for a more nuanced understanding of gene-specific regulatory mechanisms.

摘要

我们基因的调控在很大程度上依赖于增强子和启动子之间的协同通信,然而,在活跃转录过程中这种动态相互作用背后的机制仍不清楚。在这里,我们使用顺序DNA/RNA/免疫荧光-荧光原位杂交分析,研究了小鼠胚胎干细胞中与转录爆发相关的增强子-启动子(E-P)相互作用。我们的数据表明,特定基因的活跃状态以不同基因组区域之间的特定接近度和转录调节因子的积累为特征。数学模拟表明,局部粘度的增加可能有助于稳定这些E-P接近度的持续时间。我们的研究为E-P接近度、蛋白质积累和转录动态之间的关联提供了见解,为更细致地理解基因特异性调控机制铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efb1/11623302/b8b3179801d1/sciadv.adn0020-f1.jpg

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