The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
GADD45A binds R-loops and recruits TET1 to CpG island promoters
Open accessAbstract
R-loops are DNA–RNA hybrids enriched at CpG islands (CGIs) that can regulate chromatin states1–8. How R-loops are recognized and interpreted by specific epigenetic readers is unknown. Here we show that GADD45A (growth arrest and DNA damage protein 45A) binds directly to R-loops and mediates local DNA demethylation by recruiting TET1 (ten-eleven translocation 1). Studying the tumor suppressor TCF21 (ref. 9), we find that antisense long noncoding (lncRNA) TARID (TCF21 antisense RNA inducing promoter demethylation) forms an R-loop at the TCF21 promoter. Binding of GADD45A to the R-loop triggers local DNA demethylation and TCF21 expression. TARID transcription, R-loop formation, DNA demethylation, and TCF21 expression proceed sequentially during the cell cycle. Oxidized DNA demethylation intermediates are enriched at genomic R-loops and their levels increase upon RNase H1 depletion. Genomic profiling in embryonic stem cells identifies thousands of R-loop-dependent TET1 binding sites at CGIs. We propose that GADD45A is an epigenetic R-loop reader that recruits the demethylation machinery to promoter CGIs. GADD45A directly binds to R-loops and mediates local DNA demethylation by recruiting TET1. lncRNA-mediated formation of R-loops at the promoter of the tumor suppressor TCF21 triggers GADD45A binding, demethylation and expression.
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Cited by
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Statello, L., Guo, C.-J., Chen, L.-L., & Huarte, M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00315-9 · Cited by 4,991
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RNA m6A regulates transcription via DNA demethylation and chromatin accessibility
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Pachano, T., Sánchez-Gaya, V., Ealo, T., Mariner-Faulí, M., Bleckwehl, T., Asenjo, H. G., Respuela, P., Cruz-Molina, S., Muñoz-San Martín, M., Haro, E., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00888-x · Cited by 116
Metadata
- Authors
- Arab, K., Karaulanov, E., Musheev, M., Trnka, P., Schäfer, A., Grummt, I., & Niehrs, C.
- Venue
- Nature Genetics
- Published
- 2019-01-07
- Volume
- 51
- Issue
- 2
- Pages
- 217-223
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2906567604
- Cited by
- 312
- References
- 39
- FWCI
- 7.77
- Type
- journal article
- Language
- en
- Open access
- green
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