Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation
| العنوان: | Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation |
|---|---|
| المؤلفون: | Xiaoyu Zhu, Sung Yun Jung, Mingjun Bi, Joo-Hyung Lee, Michael J. Bolt, Haoyi Wu, Phuoc T. Nguyen, Naadir Jamal, Guojie Li, Michael A. Mancini, Kuang-Lei Tsai, Joanna Krakowiak, Zhijie Liu, Amedeo Caflisch, Pankaj Singh, Ruoyu Wang, Wenbo Li, Josephine C. Ferreon, Jiaofang Shao, Zian Liao, Elena V. Moroz-Omori, Caleb J. Shi, Ragini Mistry, Feng Xiong, Fabio Stossi |
| المساهمون: | University of Zurich, Li, Wenbo |
| المصدر: | Mol Cell |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Transcriptional Activation, Adenosine, 610 Medicine & health, Cell Cycle Proteins, Nerve Tissue Proteins, Enhancer RNAs, Biology, Methylation, Article, 1307 Cell Biology, Transcription (biology), Coactivator, 10019 Department of Biochemistry, 1312 Molecular Biology, Transcriptional regulation, Humans, Regulatory Elements, Transcriptional, Enhancer, Molecular Biology, Gene, Regulation of gene expression, RNA, Cell Biology, Cell biology, Enhancer Elements, Genetic, Gene Expression Regulation, 570 Life sciences, biology, RNA Splicing Factors, Transcription Factors |
| الوصف: | The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control. |
| وصف الملف: | Lee_at_al_2021-s2.0-S1097276521005931-main.pdf - application/pdf |
| تدمد: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2021.07.024 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5c0debe70b2911c4ddf6b714bd827686 https://doi.org/10.1016/j.molcel.2021.07.024 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5c0debe70b2911c4ddf6b714bd827686 |
| قاعدة البيانات: | OpenAIRE |
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