The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
R-Loop Formation Is a Distinctive Characteristic of Unmethylated Human CpG Island Promoters
Open accessAbstract
Summary CpG islands (CGIs) function as promoters for approximately 60% of human genes. Most of these elements remain protected from CpG methylation, a prevalent epigenetic modification associated with transcriptional silencing. Here, we report that methylation-resistant CGI promoters are characterized by significant strand asymmetry in the distribution of guanines and cytosines (GC skew) immediately downstream from their transcription start sites. Using innovative genomics methodologies, we show that transcription through regions of GC skew leads to the formation of long R-loop structures. Furthermore, we show that GC skew and R-loop formation potential is correlated with and predictive of the unmethylated state of CGIs. Finally, we provide evidence that R-loop formation protects from DNMT3B1, the primary de novo DNA methyltransferase in early development. Altogether, these results suggest that protection from DNA methylation is a built-in characteristic of the DNA sequence of CGI promoters that is revealed by the co-transcriptional formation of R-loop structures.
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Citations
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124
High-Resolution Profiling of Histone Methylations in the Human Genome
Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Schones, D. E., Wang, Z., Wei, G., Chepelev, I., & Zhao, K. (2007) · Cell · doi:10.1016/j.cell.2007.05.009 · Cited by 6,845
Human DNA methylomes at base resolution show widespread epigenomic differences
Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., Nery, J. R., Lee, L., Ye, Z., Ngo, Q.-M., et al. (2009) · Nature · doi:10.1038/nature08514 · Cited by 4,673
CpG islands influence chromatin structure via the CpG-binding protein Cfp1
Thomson, J. P., Skene, P. J., Selfridge, J., Clouaire, T., Guy, J., Webb, S., Kerr, A. R. W., Deaton, A., Andrews, R., James, K. D., et al. (2010) · Nature · doi:10.1038/nature08924 · Cited by 625
Transcription-associated mutational asymmetry in mammalian evolution
Program, N. C. S., Green, P., Ewing, B., Miller, W., Thomas, P. J., & Green, E. D. (2003) · Nature Genetics · doi:10.1038/ng1103 · Cited by 285 · cited 1×
“Likewise, global R loop formation is consistent with prior suggestions that the compositional asymmetries observed at human promoters are due to transcription-coupled mutational processes (Green et al., 2003; Polak and Arndt, 2008).”
Initiation of DNA replication at CpG islands in mammalian chromosomes
Delgado, S., Gómez, M., Bird, A., & Antequera, F. (1998) · The EMBO Journal · doi:10.1093/emboj/17.8.2426 · Cited by 242
Cited by
DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045
Function and information content of DNA methylation
Schübeler, D. (2015) · Nature · doi:10.1038/nature14192 · Cited by 2,060
Enhancers as non-coding RNA transcription units: recent insights and future perspectives
Li, W., Notani, D., & Rosenfeld, M. G. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.4 · Cited by 710
Born to run: control of transcription elongation by RNA polymerase II
Chen, F. X., Smith, E. R., & Shilatifard, A. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0010-5 · Cited by 447
GADD45A binds R-loops and recruits TET1 to CpG island promoters
Arab, K., Karaulanov, E., Musheev, M., Trnka, P., Schäfer, A., Grummt, I., & Niehrs, C. (2019) · Nature Genetics · doi:10.1038/s41588-018-0306-6 · Cited by 312
Metadata
- Authors
- Ginno, P. A., Lott, P. L., Christensen, H. C., Korf, I., & Chédin, F.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 45
- Issue
- 6
- Pages
- 814-825
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1967706132
- Cited by
- 910
- References
- 7
- FWCI
- 17.19
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ginno, P. A., Lott, P. L., Christensen, H. C., Korf, I., & Chédin, F. (2012). R-Loop Formation Is a Distinctive Characteristic of Unmethylated Human CpG Island Promoters. Molecular Cell. https://doi.org/10.1016/j.molcel.2012.01.017
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
