Histone H4 lysine 20 acetylation is associated with gene repression in human cells

Jun Ya Kaimori; Kazumitsu Maehara; Yoko Hayashi-Takanaka; Akihito Harada; Masafumi Fukuda; Satoko Yamamoto; Naotsugu Ichimaru; Takashi Umehara; Shigeyuki Yokoyama; Ryo Matsuda; Tsuyoshi Ikura; Koji Nagao; Chikashi Obuse; Naohito Nozaki; Shiro Takahara; Toshifumi Takao; Yasuyuki Ohkawa; Hiroshi Kimura; Yoshitaka Isaka

doi:10.1038/srep24318

Histone H4 lysine 20 acetylation is associated with gene repression in human cells

Jun Ya Kaimori, Kazumitsu Maehara, Yoko Hayashi-Takanaka, Akihito Harada, Masafumi Fukuda, Satoko Yamamoto, Naotsugu Ichimaru, Takashi Umehara, Shigeyuki Yokoyama, Ryo Matsuda, Tsuyoshi Ikura, Koji Nagao, Chikashi Obuse, Naohito Nozaki, Shiro Takahara, Toshifumi Takao, Yasuyuki Ohkawa, Hiroshi Kimura, Yoshitaka Isaka

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Abstract

Histone acetylation is generally associated with gene activation and chromatin decondensation. Recent mass spectrometry analysis has revealed that histone H4 lysine 20, a major methylation site, can also be acetylated. To understand the function of H4 lysine 20 acetylation (H4K20ac), we have developed a specific monoclonal antibody and performed ChIP-seq analysis using HeLa-S3 cells. H4K20ac was enriched around the transcription start sites (TSSs) of minimally expressed genes and in the gene body of expressed genes, in contrast to most histone acetylation being enriched around the TSSs of expressed genes. The distribution of H4K20ac showed little correlation with known histone modifications, including histone H3 methylations. A motif search in H4K20ac-enriched sequences, together with transcription factor binding profiles based on ENCODE ChIP-seq data, revealed that most transcription activators are excluded from H4K20ac-enriched genes and a transcription repressor NRSF/REST co-localized with H4K20ac. These results suggest that H4K20ac is a unique acetylation mark associated with gene repression.

Original language	English
Article number	24318
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep24318
Publication status	Published - Apr 11 2016

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Kaimori, J. Y., Maehara, K., Hayashi-Takanaka, Y., Harada, A., Fukuda, M., Yamamoto, S., Ichimaru, N., Umehara, T., Yokoyama, S., Matsuda, R., Ikura, T., Nagao, K., Obuse, C., Nozaki, N., Takahara, S., Takao, T., Ohkawa, Y., Kimura, H., & Isaka, Y. (2016). Histone H4 lysine 20 acetylation is associated with gene repression in human cells. Scientific reports, 6, Article 24318. https://doi.org/10.1038/srep24318

Kaimori, JY, Maehara, K, Hayashi-Takanaka, Y, Harada, A, Fukuda, M, Yamamoto, S, Ichimaru, N, Umehara, T, Yokoyama, S, Matsuda, R, Ikura, T, Nagao, K, Obuse, C, Nozaki, N, Takahara, S, Takao, T, Ohkawa, Y, Kimura, H & Isaka, Y 2016, 'Histone H4 lysine 20 acetylation is associated with gene repression in human cells', Scientific reports, vol. 6, 24318. https://doi.org/10.1038/srep24318

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title = "Histone H4 lysine 20 acetylation is associated with gene repression in human cells",

abstract = "Histone acetylation is generally associated with gene activation and chromatin decondensation. Recent mass spectrometry analysis has revealed that histone H4 lysine 20, a major methylation site, can also be acetylated. To understand the function of H4 lysine 20 acetylation (H4K20ac), we have developed a specific monoclonal antibody and performed ChIP-seq analysis using HeLa-S3 cells. H4K20ac was enriched around the transcription start sites (TSSs) of minimally expressed genes and in the gene body of expressed genes, in contrast to most histone acetylation being enriched around the TSSs of expressed genes. The distribution of H4K20ac showed little correlation with known histone modifications, including histone H3 methylations. A motif search in H4K20ac-enriched sequences, together with transcription factor binding profiles based on ENCODE ChIP-seq data, revealed that most transcription activators are excluded from H4K20ac-enriched genes and a transcription repressor NRSF/REST co-localized with H4K20ac. These results suggest that H4K20ac is a unique acetylation mark associated with gene repression.",

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AU - Kaimori, Jun Ya

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AU - Fukuda, Masafumi

AU - Yamamoto, Satoko

AU - Ichimaru, Naotsugu

AU - Umehara, Takashi

AU - Yokoyama, Shigeyuki

AU - Matsuda, Ryo

AU - Ikura, Tsuyoshi

AU - Nagao, Koji

AU - Obuse, Chikashi

AU - Nozaki, Naohito

AU - Takahara, Shiro

AU - Takao, Toshifumi

AU - Ohkawa, Yasuyuki

AU - Kimura, Hiroshi

AU - Isaka, Yoshitaka

PY - 2016/4/11

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N2 - Histone acetylation is generally associated with gene activation and chromatin decondensation. Recent mass spectrometry analysis has revealed that histone H4 lysine 20, a major methylation site, can also be acetylated. To understand the function of H4 lysine 20 acetylation (H4K20ac), we have developed a specific monoclonal antibody and performed ChIP-seq analysis using HeLa-S3 cells. H4K20ac was enriched around the transcription start sites (TSSs) of minimally expressed genes and in the gene body of expressed genes, in contrast to most histone acetylation being enriched around the TSSs of expressed genes. The distribution of H4K20ac showed little correlation with known histone modifications, including histone H3 methylations. A motif search in H4K20ac-enriched sequences, together with transcription factor binding profiles based on ENCODE ChIP-seq data, revealed that most transcription activators are excluded from H4K20ac-enriched genes and a transcription repressor NRSF/REST co-localized with H4K20ac. These results suggest that H4K20ac is a unique acetylation mark associated with gene repression.

AB - Histone acetylation is generally associated with gene activation and chromatin decondensation. Recent mass spectrometry analysis has revealed that histone H4 lysine 20, a major methylation site, can also be acetylated. To understand the function of H4 lysine 20 acetylation (H4K20ac), we have developed a specific monoclonal antibody and performed ChIP-seq analysis using HeLa-S3 cells. H4K20ac was enriched around the transcription start sites (TSSs) of minimally expressed genes and in the gene body of expressed genes, in contrast to most histone acetylation being enriched around the TSSs of expressed genes. The distribution of H4K20ac showed little correlation with known histone modifications, including histone H3 methylations. A motif search in H4K20ac-enriched sequences, together with transcription factor binding profiles based on ENCODE ChIP-seq data, revealed that most transcription activators are excluded from H4K20ac-enriched genes and a transcription repressor NRSF/REST co-localized with H4K20ac. These results suggest that H4K20ac is a unique acetylation mark associated with gene repression.

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Histone H4 lysine 20 acetylation is associated with gene repression in human cells

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