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

Wenyi Mi; Haipeng Guan; Jie Lyu; Dan Zhao; Yuanxin Xi; Shiming Jiang; Forest H. Andrews; Xiaolu Wang; Mihai Gagea; Hong Wen; Laszlo Tora; Sharon Y.R. Dent; Tatiana G. Kutateladze; Wei Li; Haitao Li; Xiaobing Shi

doi:10.1038/s41467-017-01173-4

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

Wenyi Mi, Haipeng Guan, Jie Lyu, Dan Zhao, Yuanxin Xi, Shiming Jiang, Forest H. Andrews, Xiaolu Wang, Mihai Gagea, Hong Wen, Laszlo Tora, Sharon Y.R. Dent, Tatiana G. Kutateladze, Wei Li, Haitao Li, Xiaobing Shi

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96 Scopus citations

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.

Original language	English (US)
Article number	1088
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-01173-4
State	Published - Dec 1 2017

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-017-01173-4

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title = "YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer",

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.",

author = "Wenyi Mi and Haipeng Guan and Jie Lyu and Dan Zhao and Yuanxin Xi and Shiming Jiang and Andrews, {Forest H.} and Xiaolu Wang and Mihai Gagea and Hong Wen and Laszlo Tora and Dent, {Sharon Y.R.} and Kutateladze, {Tatiana G.} and Wei Li and Haitao Li and Xiaobing Shi",

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AU - Mi, Wenyi

AU - Guan, Haipeng

AU - Lyu, Jie

AU - Zhao, Dan

AU - Xi, Yuanxin

AU - Jiang, Shiming

AU - Andrews, Forest H.

AU - Wang, Xiaolu

AU - Gagea, Mihai

AU - Wen, Hong

AU - Tora, Laszlo

AU - Dent, Sharon Y.R.

AU - Kutateladze, Tatiana G.

AU - Li, Wei

AU - Li, Haitao

AU - Shi, Xiaobing

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

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

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MD Anderson CCSG core facilities

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