RNA m6A regulates transcription via DNA demethylation and chromatin accessibility
Abstract
Transcriptional regulation, which integrates chromatin accessibility, transcription factors and epigenetic modifications, is crucial for establishing and maintaining cell identity. The interplay between different epigenetic modifications and its contribution to transcriptional regulation remains elusive. Here, we show that METTL3-mediated RNA N 6 -methyladenosine (m 6 A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m 6 A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m 6 A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. Therefore, we have characterized a regulatory mechanism of chromatin accessibility and gene transcription mediated by RNA m 6 A formation coupled with DNA demethylation, highlighting the importance of the crosstalk between RNA m 6 A and DNA modification in physiologic and pathogenic process.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
METTL3-dependent m6A modifications have been implicated in regulation of chromatin accessibility.
“Since METTL3-dependent m6A modifications have been implicated in regulation of chromatin accessibility (Deng et al., 2022)”
From METTL3 uncouples chromatin accessibility from transcription during retinal development (2025) · cites this paper as Deng et al., 2022
Cites
Regulation of chromatin by histone modifications
Bannister, A. J., & Kouzarides, T. (2011) · Cell Research · doi:10.1038/cr.2011.22 · Cited by 6,012 · see citing works
DNA methylation landscapes: Provocative insights from epigenomics
Suzuki, M. M., & Bird, A. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2341 · Cited by 3,039 · see citing works
Linking DNA methylation and histone modification: patterns and paradigms
Cedar, H., & Bergman, Y. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2540 · Cited by 2,267 · see citing works
Chromatin accessibility and the regulatory epigenome
Klemm, S. L., Shipony, Z., & Greenleaf, W. J. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-018-0089-8 · Cited by 1,793 · see citing works
Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally
Huang, H., Weng, H., Zhou, K., Wu, T., Zhao, B. S., Sun, M., Chen, Z., Deng, X., Xiao, G., Auer, F., et al. (2019) · Nature · doi:10.1038/s41586-019-1016-7 · Cited by 677 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Analog epigenetic memory revealed by targeted chromatin editing
Palacios, S., Bruno, S., Weiss, R., Salibi, E., Kane, A., Ilia, K., & Del Vecchio, D. (2024) · doi:10.1101/2024.02.13.580200 · Cited by 13 · see citing works
A multiomics approach reveals RNA dynamics promote cellular sensitivity to DNA hypomethylation
Ge, A. Y., Arab, A., Dai, R., Navickas, A., Fish, L., Garcia, K., Asgharian, H., Goudreau, J., Lee, S., Keenan, K., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-77314-9 · Cited by 4 · see citing works
METTL3 uncouples chromatin accessibility from transcription during retinal development
Xu, J., Huang, Y., Han, Z., Li, Q., Liu, J., & Rao, R. C. (2025) · Stem Cell Reports · doi:10.1016/j.stemcr.2025.102690 · Cited by 1 · see citing works
- Authors
- Deng, S., Zhang, J., Su, J., Zuo, Z., Zeng, L., Liu, K., Zheng, Y., Huang, X., Bai, R., Zhuang, L., Ye, Y., Li, M., Pan, L., Deng, J., Wu, G., Li, R., Zhang, S., Wu, C., Lin, D., Chen, J., & Zheng, J.
- Affiliations
- Sun Yat-sen University Cancer Center (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- City Of Hope National Medical Center (US)
- Corresponding author
- Lin, Dongxin
- Chen, Jianjun
- Zheng, Jian
- ORCID
- Venue
- Nature Genetics
- Published
- 2022-09
- Volume
- 54
- Issue
- 9
- Pages
- 1427-1437
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W4294904827
- Cited by
- 187
- References
- 5
- Citations by year
- 2026: 40 · 2025: 53 · 2024: 49 · 2023: 40 · 2022: 5
- FWCI
- 12.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Guangdong Innovative and Entrepreneurial Research Team Program (2017ZT07S096)
- National Natural Science Foundation of China (82072617, 81772586)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- METTL3, DNA demethylation, chromatin accessibility, FXR1, TET1, transcriptional regulation, epigenetic regulation, cancer cells, gene transcription
- MeSH terms
- DNA Demethylation, Chromatin, DNA, RNA, Transcription Factors, DNA Methylation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
