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Nat Commun. 2017 Oct 20;8(1):1088. doi: 10.1038/s41467-017-01173-4.

YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer.

Mi W1,2, Guan H3,4, Lyu J5, Zhao D3,4, Xi Y5, Jiang S1,2, Andrews FH6, Wang X1,2, Gagea M7, Wen H1,2, Tora L8,9,10,11, Dent SYR1,2,12, Kutateladze TG6, Li W13, Li H14,15, Shi X16,17,18.

Author information

1
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
2
Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
3
MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China.
4
Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
5
Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
6
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
7
Department of Veterinary Medicine & Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
8
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404, Illkirch, France.
9
Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France.
10
Institut National de la Santé et de la Recherche Médicale, U964, 67404, Illkirch, France.
11
Université de Strasbourg, 67404, Illkirch, France.
12
Genes and Development and Epigenetics & Molecular Carcinogenesis Graduate Programs, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, 77030, USA.
13
Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA. wl1@bcm.edu.
14
MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084, China. lht@tsinghua.edu.cn.
15
Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, 100084, China. lht@tsinghua.edu.cn.
16
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA. xbshi@mdanderson.org.
17
Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA. xbshi@mdanderson.org.
18
Genes and Development and Epigenetics & Molecular Carcinogenesis Graduate Programs, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, 77030, USA. xbshi@mdanderson.org.

Abstract

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.

PMID:
29057918
PMCID:
PMC5651844
DOI:
10.1038/s41467-017-01173-4
[Indexed for MEDLINE]
Free PMC Article

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