Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally

Huilin Huang, Hengyou Weng, Keren Zhou, Tong Wu, Boxuan Simen Zhao, Mingli Sun, Zhenhua Chen, Xiaolan Deng, Gang Xiao, Franziska Auer, Lars Klemm, Huizhe Wu, Zhixiang Zuo, Xi Qin, Yunzhu Dong, Yile Zhou, Hanjun Qin, Shu Tao, Juan Du, Jun Liu, Zhike Lu, Hang Yin, Ana Mesquita, Celvie L. Yuan, Yueh-Chiang Hu, Wenju Sun, Rui Su, Lei Dong, Chao Shen, Chenying Li, Ying Qing, Xi Jiang, Xiwei Wu, Miao Sun, Jun-Lin Guan, Lianghu Qu, Minjie Wei, Markus Müschen, Gang Huang (), Chuan He (), Jianhua Yang () and Jianjun Chen ()
Additional contact information
Huilin Huang: Beckman Research Institute of City of Hope
Hengyou Weng: Beckman Research Institute of City of Hope
Keren Zhou: Sun Yat-sen University
Tong Wu: University of Chicago
Boxuan Simen Zhao: University of Chicago
Mingli Sun: Beckman Research Institute of City of Hope
Zhenhua Chen: Beckman Research Institute of City of Hope
Xiaolan Deng: Beckman Research Institute of City of Hope
Gang Xiao: Beckman Research Institute of City of Hope
Franziska Auer: Beckman Research Institute of City of Hope
Lars Klemm: Beckman Research Institute of City of Hope
Huizhe Wu: Beckman Research Institute of City of Hope
Zhixiang Zuo: University of Cincinnati College of Medicine
Xi Qin: Beckman Research Institute of City of Hope
Yunzhu Dong: Cincinnati Children’s Hospital Medical Center
Yile Zhou: Cincinnati Children’s Hospital Medical Center
Hanjun Qin: Beckman Research Institute of City of Hope
Shu Tao: Beckman Research Institute of City of Hope
Juan Du: Beckman Research Institute of City of Hope
Jun Liu: University of Chicago
Zhike Lu: University of Chicago
Hang Yin: University of Chicago
Ana Mesquita: University of Cincinnati College of Medicine
Celvie L. Yuan: Cincinnati Children’s Hospital Medical Center
Yueh-Chiang Hu: Cincinnati Children’s Hospital Medical Center
Wenju Sun: Sun Yat-sen University
Rui Su: Beckman Research Institute of City of Hope
Lei Dong: Beckman Research Institute of City of Hope
Chao Shen: Beckman Research Institute of City of Hope
Chenying Li: Beckman Research Institute of City of Hope
Ying Qing: Beckman Research Institute of City of Hope
Xi Jiang: Beckman Research Institute of City of Hope
Xiwei Wu: Beckman Research Institute of City of Hope
Miao Sun: University of Cincinnati College of Medicine
Jun-Lin Guan: University of Cincinnati College of Medicine
Lianghu Qu: Sun Yat-sen University
Minjie Wei: School of Pharmacy, China Medical University
Markus Müschen: Beckman Research Institute of City of Hope
Gang Huang: Cincinnati Children’s Hospital Medical Center
Chuan He: University of Chicago
Jianhua Yang: Sun Yat-sen University
Jianjun Chen: Beckman Research Institute of City of Hope

Nature, 2019, vol. 567, issue 7748, 414-419

Abstract: Abstract DNA and histone modifications have notable effects on gene expression1. Being the most prevalent internal modification in mRNA, the N6-methyladenosine (m6A) mRNA modification is as an important post-transcriptional mechanism of gene regulation2–4 and has crucial roles in various normal and pathological processes5–12. However, it is unclear how m6A is specifically and dynamically deposited in the transcriptome. Here we report that histone H3 trimethylation at Lys36 (H3K36me3), a marker for transcription elongation, guides m6A deposition globally. We show that m6A modifications are enriched in the vicinity of H3K36me3 peaks, and are reduced globally when cellular H3K36me3 is depleted. Mechanistically, H3K36me3 is recognized and bound directly by METTL14, a crucial component of the m6A methyltransferase complex (MTC), which in turn facilitates the binding of the m6A MTC to adjacent RNA polymerase II, thereby delivering the m6A MTC to actively transcribed nascent RNAs to deposit m6A co-transcriptionally. In mouse embryonic stem cells, phenocopying METTL14 knockdown, H3K36me3 depletion also markedly reduces m6A abundance transcriptome-wide and in pluripotency transcripts, resulting in increased cell stemness. Collectively, our studies reveal the important roles of H3K36me3 and METTL14 in determining specific and dynamic deposition of m6A in mRNA, and uncover another layer of gene expression regulation that involves crosstalk between histone modification and RNA methylation.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (8)

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1016-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:567:y:2019:i:7748:d:10.1038_s41586-019-1016-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-1016-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().