The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects
Open accessAbstract
Comprehensive sequencing of human cancers has identified recurrent mutations in genes encoding chromatin regulatory proteins. For clear cell renal cell carcinoma (ccRCC), three of the five commonly mutated genes encode the chromatin regulators PBRM1, SETD2, and BAP1. How these mutations alter the chromatin landscape and transcriptional program in ccRCC or other cancers is not understood. Here, we identified alterations in chromatin organization and transcript profiles associated with mutations in chromatin regulators in a large cohort of primary human kidney tumors. By associating variation in chromatin organization with mutations in SETD2, which encodes the enzyme responsible for H3K36 trimethylation, we found that changes in chromatin accessibility occurred primarily within actively transcribed genes. This increase in chromatin accessibility was linked with widespread alterations in RNA processing, including intron retention and aberrant splicing, affecting ∼25% of all expressed genes. Furthermore, decreased nucleosome occupancy proximal to misspliced exons was observed in tumors lacking H3K36me3. These results directly link mutations in SETD2 to chromatin accessibility changes and RNA processing defects in cancer. Detecting the functional consequences of specific mutations in chromatin regulatory proteins in primary human samples could ultimately inform the therapeutic application of an emerging class of chromatin-targeted compounds.
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Cites
Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113205 · Cited by 7,774
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
GREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502
The accessible chromatin landscape of the human genome
Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., et al. (2012) · Nature · doi:10.1038/nature11232 · Cited by 2,679
Self-citationMapSplice: Accurate mapping of RNA-seq reads for splice junction discovery
Wang, K., Singh, D., Zeng, Z., Coleman, S. J., Huang, Y., Savich, G. L., He, X., Mieczkowski, P., Grimm, S. A., Perou, C. M., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq622 · Cited by 1,193
Self-citationSystematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
Dalgliesh, G. L., Furge, K., Greenman, C., Chen, L., Bignell, G., Butler, A., Davies, H., Edkins, S., Hardy, C., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08672 · Cited by 1,173 · cited 7×
“For clear cell renal cell carcinoma (ccRCC), three of the five commonly mutated genes encode the chromatin regulators PBRM1, SETD2, and BAP1.”
BackgroundInfluentialHigh-resolution genome-wide mapping of HIF-binding sites by ChIP-seq
Schödel, J., Oikonomopoulos, S., Ragoussis, J., Pugh, C. W., Ratcliffe, P. J., & Mole, D. R. (2011) · Blood · doi:10.1182/blood-2010-10-314427 · Cited by 724
Chromatin organization marks exon-intron structure
Schwartz, S., Meshorer, E., & Ast, G. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1659 · Cited by 638
Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation
Edmunds, J. W., Mahadevan, L. C., & Clayton, A. L. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601967 · Cited by 547
The human SWI/SNF subunit Brm is a regulator of alternative splicing
Batsché, E., Yaniv, M., & Muchardt, C. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1030 · Cited by 471
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Therapeutic targeting of splicing in cancer
Lee, S. C.-W., & Abdel-Wahab, O. (2016) · Nature Medicine · doi:10.1038/nm.4165 · Cited by 561
Regulation of Alternative Splicing Through Coupling with Transcription and Chromatin Structure
Naftelberg, S., Schor, I. E., Ast, G., & Kornblihtt, A. R. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034242 · Cited by 448
Simon, J. M., Giresi, P. G., Davis, I. J., & Lieb, J. D. (2012) · Nature Protocols · doi:10.1038/nprot.2011.444 · Cited by 329
Self-citationCoupling of RNA Polymerase II Transcription Elongation with Pre-mRNA Splicing
Saldi, T., Cortazar, M. A., Sheridan, R. M., & Bentley, D. L. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.04.017 · Cited by 258
Metadata
- Authors
- Simon, J. M., Hacker, K. E., Singh, D., Brannon, A. R., Parker, J. S., Weiser, M., Ho, T. H., Kuan, P.-F., Jonasch, E., Furey, T. S., Prins, J. F., Lieb, J. D., Rathmell, W. K., & Davis, I. J.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-10-24
- Volume
- 24
- Issue
- 2
- Pages
- 241-250
- ISSN
- 1088-9051 (ISSN-L)
- OpenAlex
- W4299652198
- Cited by
- 189
- References
- 11
- Type
- posted content
- Language
- en
- Open access
- bronze
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- Simon, J. M., Hacker, K. E., Singh, D., Brannon, A. R., Parker, J. S., Weiser, M., Ho, T. H., Kuan, P.-F., Jonasch, E., Furey, T. S., Prins, J. F., Lieb, J. D., Rathmell, W. K., & Davis, I. J. (2014). Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects. Genome Research. https://doi.org/10.1101/gr.158253.113
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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
