Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation

Brianna J. Klein; Suk Min Jang; Catherine Lachance; Wenyi Mi; Jie Lyu; Shun Sakuraba; Krzysztof Krajewski; Wesley W. Wang; Simone Sidoli; Jiuyang Liu; Yi Zhang; Xiaolu Wang; Becka M. Warfield; Andrew J. Kueh; Anne K. Voss; Tim Thomas; Benjamin A. Garcia; Wenshe R. Liu; Brian D. Strahl; Hidetoshi Kono; Wei Li; Xiaobing Shi; Jacques Côté; Tatiana G. Kutateladze

doi:10.1038/s41467-019-12551-5

Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation

Brianna J. Klein, Suk Min Jang, Catherine Lachance, Wenyi Mi, Jie Lyu, Shun Sakuraba, Krzysztof Krajewski, Wesley W. Wang, Simone Sidoli, Jiuyang Liu, Yi Zhang, Xiaolu Wang, Becka M. Warfield, Andrew J. Kueh, Anne K. Voss, Tim Thomas, Benjamin A. Garcia, Wenshe R. Liu, Brian D. Strahl, Hidetoshi KonoWei Li, Xiaobing Shi, Jacques Côté, Tatiana G. Kutateladze

Biochemistry

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORF_DPF). The crystal structure of MORF_DPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORF_DPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORF_DPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.

Original language	English (US)
Article number	4724
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12551-5
State	Published - Dec 1 2019

ASJC Scopus subject areas

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

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10.1038/s41467-019-12551-5

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Klein, B. J., Jang, S. M., Lachance, C., Mi, W., Lyu, J., Sakuraba, S., Krajewski, K., Wang, W. W., Sidoli, S., Liu, J., Zhang, Y., Wang, X., Warfield, B. M., Kueh, A. J., Voss, A. K., Thomas, T., Garcia, B. A., Liu, W. R., Strahl, B. D., ... Kutateladze, T. G. (2019). Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation. Nature communications, 10(1), Article 4724. https://doi.org/10.1038/s41467-019-12551-5

Klein, BJ, Jang, SM, Lachance, C, Mi, W, Lyu, J, Sakuraba, S, Krajewski, K, Wang, WW, Sidoli, S, Liu, J, Zhang, Y, Wang, X, Warfield, BM, Kueh, AJ, Voss, AK, Thomas, T, Garcia, BA, Liu, WR, Strahl, BD, Kono, H, Li, W, Shi, X, Côté, J & Kutateladze, TG 2019, 'Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation', Nature communications, vol. 10, no. 1, 4724. https://doi.org/10.1038/s41467-019-12551-5

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title = "Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation",

abstract = "Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.",

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doi = "10.1038/s41467-019-12551-5",

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AU - Klein, Brianna J.

AU - Jang, Suk Min

AU - Lachance, Catherine

AU - Mi, Wenyi

AU - Lyu, Jie

AU - Sakuraba, Shun

AU - Krajewski, Krzysztof

AU - Wang, Wesley W.

AU - Sidoli, Simone

AU - Liu, Jiuyang

AU - Zhang, Yi

AU - Wang, Xiaolu

AU - Warfield, Becka M.

AU - Kueh, Andrew J.

AU - Voss, Anne K.

AU - Thomas, Tim

AU - Garcia, Benjamin A.

AU - Liu, Wenshe R.

AU - Strahl, Brian D.

AU - Kono, Hidetoshi

AU - Li, Wei

AU - Shi, Xiaobing

AU - Côté, Jacques

AU - Kutateladze, Tatiana G.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.

AB - Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.

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Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation

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