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PHD Finger Recognition of Unmodified Histone H3R2 Links UHRF1 to Regulation of Euchromatic Gene Expression
Open accessAbstract
SUMMARY Histone methylation occurs on both lysine and arginine residues, and its dynamic regulation plays a critical role in chromatin biology. Here we identify the UHRF1 PHD finger (PHDUHRF1), an important regulator of DNA CpG methylation, as a histone H3 unmodified arginine 2 (H3R2) recognition modality. This conclusion is based on binding studies and cocrystal structures of PHDUHRF1 bound to histone H3 peptides, where the guanidinium group of unmodified R2 forms an extensive intermolecular hydrogen bond network, with methylation of H3R2, but not H3K4 or H3K9, disrupting complex formation. We have identified direct target genes of UHRF1 from microarray and ChIP studies. Importantly, we show that UHRF1's ability to repress its direct target gene expression is dependent on PHDUHRF1 binding to unmodified H3R2, thereby demonstrating the functional importance of this recognition event and supporting the potential for crosstalk between histone arginine methylation and UHRF1 function.
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Citations
Cited by
Histone methylation: a dynamic mark in health, disease and inheritance
Greer, E. L., & Shi, Y. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3173 · Cited by 2,241
Self-citationDNA methylation pathways and their crosstalk with histone methylation
Du, J., Johnson, L. M., Jacobsen, S. E., & Patel, D. J. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4043 · Cited by 1,000
Self-citationDu, J., Zhong, X., Bernatavichute, Y. V., Stroud, H., Feng, S., Caro, E., Vashisht, A. A., Terragni, J., Chin, H. G., Tu, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.07.034 · Cited by 555
Self-citationHistones: At the Crossroads of Peptide and Protein Chemistry
Müller, M. M., & Muir, T. W. (2015) · Chemical Reviews · doi:10.1021/cr5003529 · Cited by 247
The interplay between DNA and histone methylation: molecular mechanisms and disease implications
Li, Y., Chen, X., & Lu, C. (2021) · The EMBO Reports · doi:10.15252/embr.202051803 · Cited by 223
Metadata
- Authors
- Rajakumara, E., Wang, Z., Ma, H., Hu, L., Chen, H., Lin, Y., Guo, R., Wu, F., Li, H., Lan, F., Shi, Y. G., Xu, Y., Patel, D. J., & Shi, Y.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 43
- Issue
- 2
- Pages
- 275-284
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2006410633
- Cited by
- 208
- References
- 0
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Rajakumara, E., Wang, Z., Ma, H., Hu, L., Chen, H., Lin, Y., Guo, R., Wu, F., Li, H., Lan, F., Shi, Y. G., Xu, Y., Patel, D. J., & Shi, Y. (2011). PHD Finger Recognition of Unmodified Histone H3R2 Links UHRF1 to Regulation of Euchromatic Gene Expression. Molecular Cell. https://doi.org/10.1016/j.molcel.2011.07.006
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