The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain
Open accessAbstract
Background: 5-methylcytosine (mC) can be oxidized by the tet methylcytosine dioxygenase (Tet) family of enzymes to 5-hydroxymethylcytosine (hmC), which is an intermediate of mC demethylation and may also be a stable epigenetic modification that influences chromatin structure. hmC is particularly abundant in mammalian brains but its function is currently unknown. A high-resolution hydroxymethylome map is required to fully understand the function of hmC in the human brain. Results: We present genome-wide and single-base resolution maps of hmC and mC in the human brain by combined application of Tet-assisted bisulfite sequencing and bisulfite sequencing. We demonstrate that hmCs increase markedly from the fetal to the adult stage, and in the adult brain, 13% of all CpGs are highly hydroxymethylated with strong enrichment at genic regions and distal regulatory elements. Notably, hmC peaks are identified at the 5′splicing sites at the exon-intron boundary, suggesting a mechanistic link between hmC and splicing. We report a surprising transcription-correlated hmC bias toward the sense strand and an mC bias toward the antisense strand of gene bodies. Furthermore, hmC is negatively correlated with H3K27me3-marked and H3K9me3-marked repressive genomic regions, and is more enriched at poised enhancers than active enhancers. Conclusions: We provide single-base resolution hmC and mC maps in the human brain and our data imply novel roles of hmC in regulating splicing and gene expression. Hydroxymethylation is the main modification status for a large portion of CpGs situated at poised enhancers and actively transcribed regions, suggesting its roles in epigenetic tuning at these regions.
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Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
Functions of DNA methylation: islands, start sites, gene bodies and beyond
Jones, P. A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3230 · Cited by 6,061
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., et al. (2009) · Science · doi:10.1126/science.1170116 · Cited by 5,836
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
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302
Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine
Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C., & Zhang, Y. (2011) · Science · doi:10.1126/science.1210597 · Cited by 3,451
Self-citationCahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129
Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA
He, Y.-F., Li, B.-Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., et al. (2011) · Science · doi:10.1126/science.1210944 · Cited by 2,770
Self-citationThe Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
Kriaucionis, S., & Heintz, N. (2009) · Science · doi:10.1126/science.1169786 · Cited by 2,700
Global epigenomic reconfiguration during mammalian brain development
Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., et al. (2013) · Science · doi:10.1126/science.1237905 · Cited by 1,830
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Ferrucci, L., Gonzalez‐Freire, M., Fabbri, E., Simonsick, E., Tanaka, T., Moore, Z., Salimi, S., Sierra, F., & de Cabo, R. (2020) · Aging Cell · doi:10.1111/acel.13080 · Cited by 781
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Zhang, W., Li, J., Suzuki, K., Qu, J., Wang, P., Zhou, J., Liu, X., Ren, R., Xu, X., Ocampo, A., et al. (2015) · Science · doi:10.1126/science.aaa1356 · Cited by 551
Self-citationBisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution
Liu, Y., Siejka-Zielińska, P., Velikova, G., Bi, Y., Yuan, F., Tomkova, M., Bai, C., Chen, L., Schuster-Böckler, B., & Song, C.-X. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0041-2 · Cited by 472
Self-citationCpG and non-CpG methylation in epigenetic gene regulation and brain function
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Metadata
- Authors
- Wen, L., Li, X., Yan, L., Tan, Y., Li, R., Zhao, Y., Wang, Y., Xie, J., Zhang, Y., Song, C., Yu, M., Liu, X., Zhu, P., Li, X., Hou, Y., Guo, H., Wu, X., He, C., Li, R., Tang, F., & Qiao, J.
- Venue
- Genome Biology
- Published
- 2014-03-04
- Volume
- 15
- Issue
- 3
- Pages
- R49-R49
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- OpenAlex
- W2159433569
- Cited by
- 294
- References
- 49
- FWCI
- 16.06
- Type
- journal article
- Language
- en
- Open access
- gold
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- Wen, L., Li, X., Yan, L., Tan, Y., Li, R., Zhao, Y., Wang, Y., Xie, J., Zhang, Y., Song, C., Yu, M., Liu, X., Zhu, P., Li, X., Hou, Y., Guo, H., Wu, X., He, C., Li, R., . . . Qiao, J. (2014). Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain. Genome Biology. https://doi.org/10.1186/gb-2014-15-3-r49
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