YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer
Open accessAbstract
Recognition of modified histones by “reader” proteins constitutes a key mechanism regulating diverse chromatin-associated processes important for normal and neoplastic development. We recently identified the YEATS domain as a novel acetyllysine-binding module; however, the functional importance of YEATS domain-containing proteins in human cancer remains largely unknown. Here, we show that the YEATS2 gene is highly amplified in human non-small cell lung cancer (NSCLC) and is required for cancer cell growth and survival. YEATS2 binds to acetylated histone H3 via its YEATS domain. The YEATS2-containing ATAC complex co-localizes with H3K27 acetylation (H3K27ac) on the promoters of actively transcribed genes. Depletion of YEATS2 or disruption of the interaction between its YEATS domain and acetylated histones reduces the ATAC complex-dependent promoter H3K9ac levels and deactivates the expression of essential genes. Taken together, our study identifies YEATS2 as a histone H3K27ac reader that regulates a transcriptional program essential for NSCLC tumorigenesis.
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IDH-mutant cells display reduced DNA repair kinetics, accumulate DNA double stranded breaks, and are sensitized to alkylating agents.
“Indeed, IDH-mutant cells display reduced DNA repair kinetics, accumulate DNA double stranded breaks (DSBs) and are sensitized to alkylating agents131,174.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [174]
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References 58 · Cited by 159
Research works printed but not linked: 1
- [35]Dai LZ Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark Nat. Chem. Biol. 2014 10 365 U73 10.1038/nchembio.1497 24681537 · DOI
- Authors
- Mi, W., Guan, H., Lyu, J., Zhao, D., Xi, Y., Jiang, S., Andrews, F. H., Wang, X., Gagea, M., Wen, H., Tora, L., Dent, S. Y. R., Kutateladze, T. G., Li, W., Li, H., & Shi, X.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Center for Life Sciences (CN)
- Baylor College of Medicine (US)
- University of Colorado Anschutz (US)
- Corresponding author
- Li, Wei
- Li, Haitao
- Shi, Xiaobing
- ORCID
- Venue
- Nature Communications
- Published
- 2017-10-20
- Volume
- 8
- Issue
- 1
- Pages
- 1088-1088
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5651844
- OpenAlex
- W2767204171
- Cited by
- 159
- References
- 58
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 23 · 2023: 31 · 2022: 23 · 2021: 19 · 2020: 16 · 2019: 8 · 2018: 7
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Cancer Prevention and Research Institute of Texas (RP160237, RP140323, RP110471, RP150292, RP120348)
- National Natural Science Foundation of China (91519304)
- Tsinghua University
- National Institutes of Health (RP120348)
- National Postdoctoral Program for Innovative Talents (BX201600088)
- National Human Genome Research Institute (R01HG007538)
- National Cancer Institute (R01CA204020, R01CA193466)
- National Institute of General Medical Sciences (R01GM067718, R01GM100907)
- FP7 Ideas: European Research Council (340551)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- histone acetylation, non-small cell lung cancer, H3K27 acetylation, H3K9 acetylation, histone reader proteins, histone H3, gene amplification, carcinogenesis, transcriptional regulation, promoter acetylation
- MeSH terms
- Acetylation, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, Histones, Humans, Lung Neoplasms, Protein Processing, Post-Translational, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Carcinogenesis
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