LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA

Keiichi Izumikawa, Hideaki Ishikawa, Harunori Yoshikawa, Sally Fujiyama, Akira Watanabe, Hiroyuki Aburatani, Hiroyuki Tachikawa, Toshiya Hayano, Yutaka Miura, Toshiaki Isobe, Richard J. Simpson, Li Li, Jinrong Min, Nobuhiro Takahashi (Lead / Corresponding author)

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Abstract

Activation of ribosomal RNA (rRNA) synthesis is pivotal during cell growth and proliferation, but its aberrant upregulation may promote tumorigenesis. Here, we demonstrate that the candidate oncoprotein, LYAR, enhances ribosomal DNA (rDNA) transcription. Our data reveal that LYAR binds the histone-associated protein BRD2 without involvement of acetyl-lysine-binding bromodomains and recruits BRD2 to the rDNA promoter and transcribed regions via association with upstream binding factor. We show that BRD2 is required for the recruitment of the MYST-type acetyltransferase KAT7 to rDNA loci, resulting in enhanced local acetylation of histone H4. In addition, LYAR binds a complex of BRD4 and KAT7, which is then recruited to rDNA independently of the BRD2-KAT7 complex to accelerate the local acetylation of both H4 and H3. BRD2 also helps recruit BRD4 to rDNA. By contrast, LYAR has no effect on rDNA methylation or the binding of RNA polymerase I subunits to rDNA. These data suggest that LYAR promotes the association of the BRD2-KAT7 and BRD4-KAT7 complexes with transcription-competent rDNA loci but not to transcriptionally silent rDNA loci, thereby increasing rRNA synthesis by altering the local acetylation status of histone H3 and H4.

Original languageEnglish
Pages (from-to)10357-10372
Number of pages16
JournalNucleic Acids Research
Volume47
Issue number19
Early online date2 Sep 2019
DOIs
Publication statusPublished - 4 Nov 2019

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Acetyltransferases
Ribosomal RNA
Ribosomal DNA
Histones
Acetylation
Oncogene Proteins
DNA Methylation
Genetic Promoter Regions
Lysine
Carcinogenesis
Up-Regulation
Cell Proliferation

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Izumikawa, K., Ishikawa, H., Yoshikawa, H., Fujiyama, S., Watanabe, A., Aburatani, H., ... Takahashi, N. (2019). LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA. Nucleic Acids Research, 47(19), 10357-10372. https://doi.org/10.1093/nar/gkz747
Izumikawa, Keiichi ; Ishikawa, Hideaki ; Yoshikawa, Harunori ; Fujiyama, Sally ; Watanabe, Akira ; Aburatani, Hiroyuki ; Tachikawa, Hiroyuki ; Hayano, Toshiya ; Miura, Yutaka ; Isobe, Toshiaki ; Simpson, Richard J. ; Li, Li ; Min, Jinrong ; Takahashi, Nobuhiro. / LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA. In: Nucleic Acids Research. 2019 ; Vol. 47, No. 19. pp. 10357-10372.
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abstract = "Activation of ribosomal RNA (rRNA) synthesis is pivotal during cell growth and proliferation, but its aberrant upregulation may promote tumorigenesis. Here, we demonstrate that the candidate oncoprotein, LYAR, enhances ribosomal DNA (rDNA) transcription. Our data reveal that LYAR binds the histone-associated protein BRD2 without involvement of acetyl-lysine-binding bromodomains and recruits BRD2 to the rDNA promoter and transcribed regions via association with upstream binding factor. We show that BRD2 is required for the recruitment of the MYST-type acetyltransferase KAT7 to rDNA loci, resulting in enhanced local acetylation of histone H4. In addition, LYAR binds a complex of BRD4 and KAT7, which is then recruited to rDNA independently of the BRD2-KAT7 complex to accelerate the local acetylation of both H4 and H3. BRD2 also helps recruit BRD4 to rDNA. By contrast, LYAR has no effect on rDNA methylation or the binding of RNA polymerase I subunits to rDNA. These data suggest that LYAR promotes the association of the BRD2-KAT7 and BRD4-KAT7 complexes with transcription-competent rDNA loci but not to transcriptionally silent rDNA loci, thereby increasing rRNA synthesis by altering the local acetylation status of histone H3 and H4.",
author = "Keiichi Izumikawa and Hideaki Ishikawa and Harunori Yoshikawa and Sally Fujiyama and Akira Watanabe and Hiroyuki Aburatani and Hiroyuki Tachikawa and Toshiya Hayano and Yutaka Miura and Toshiaki Isobe and Simpson, {Richard J.} and Li Li and Jinrong Min and Nobuhiro Takahashi",
note = "Funding - Scientific Research, Ministry of Education, Culture, Sports, Science & Technology of Japan (MEXT) [24241075 to N.T.]; Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency (JST) [JPMJCR13M2 to I.T. and N.T.]; Naito Foundation Grant for Studying Overseas (2013) [2013-413 to H.Y.]; Uehara Memorial Foundation Postdoctoral Fellowship [201430061 to H.Y.]; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Individual Fellowship [657087 to H.Y]. Funding for open access charge: JST CREST.",
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Izumikawa, K, Ishikawa, H, Yoshikawa, H, Fujiyama, S, Watanabe, A, Aburatani, H, Tachikawa, H, Hayano, T, Miura, Y, Isobe, T, Simpson, RJ, Li, L, Min, J & Takahashi, N 2019, 'LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA', Nucleic Acids Research, vol. 47, no. 19, pp. 10357-10372. https://doi.org/10.1093/nar/gkz747

LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA. / Izumikawa, Keiichi; Ishikawa, Hideaki; Yoshikawa, Harunori; Fujiyama, Sally; Watanabe, Akira; Aburatani, Hiroyuki; Tachikawa, Hiroyuki; Hayano, Toshiya; Miura, Yutaka; Isobe, Toshiaki; Simpson, Richard J.; Li, Li; Min, Jinrong; Takahashi, Nobuhiro (Lead / Corresponding author).

In: Nucleic Acids Research, Vol. 47, No. 19, 04.11.2019, p. 10357-10372.

Research output: Contribution to journalArticle

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T1 - LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA

AU - Izumikawa, Keiichi

AU - Ishikawa, Hideaki

AU - Yoshikawa, Harunori

AU - Fujiyama, Sally

AU - Watanabe, Akira

AU - Aburatani, Hiroyuki

AU - Tachikawa, Hiroyuki

AU - Hayano, Toshiya

AU - Miura, Yutaka

AU - Isobe, Toshiaki

AU - Simpson, Richard J.

AU - Li, Li

AU - Min, Jinrong

AU - Takahashi, Nobuhiro

N1 - Funding - Scientific Research, Ministry of Education, Culture, Sports, Science & Technology of Japan (MEXT) [24241075 to N.T.]; Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency (JST) [JPMJCR13M2 to I.T. and N.T.]; Naito Foundation Grant for Studying Overseas (2013) [2013-413 to H.Y.]; Uehara Memorial Foundation Postdoctoral Fellowship [201430061 to H.Y.]; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Individual Fellowship [657087 to H.Y]. Funding for open access charge: JST CREST.

PY - 2019/11/4

Y1 - 2019/11/4

N2 - Activation of ribosomal RNA (rRNA) synthesis is pivotal during cell growth and proliferation, but its aberrant upregulation may promote tumorigenesis. Here, we demonstrate that the candidate oncoprotein, LYAR, enhances ribosomal DNA (rDNA) transcription. Our data reveal that LYAR binds the histone-associated protein BRD2 without involvement of acetyl-lysine-binding bromodomains and recruits BRD2 to the rDNA promoter and transcribed regions via association with upstream binding factor. We show that BRD2 is required for the recruitment of the MYST-type acetyltransferase KAT7 to rDNA loci, resulting in enhanced local acetylation of histone H4. In addition, LYAR binds a complex of BRD4 and KAT7, which is then recruited to rDNA independently of the BRD2-KAT7 complex to accelerate the local acetylation of both H4 and H3. BRD2 also helps recruit BRD4 to rDNA. By contrast, LYAR has no effect on rDNA methylation or the binding of RNA polymerase I subunits to rDNA. These data suggest that LYAR promotes the association of the BRD2-KAT7 and BRD4-KAT7 complexes with transcription-competent rDNA loci but not to transcriptionally silent rDNA loci, thereby increasing rRNA synthesis by altering the local acetylation status of histone H3 and H4.

AB - Activation of ribosomal RNA (rRNA) synthesis is pivotal during cell growth and proliferation, but its aberrant upregulation may promote tumorigenesis. Here, we demonstrate that the candidate oncoprotein, LYAR, enhances ribosomal DNA (rDNA) transcription. Our data reveal that LYAR binds the histone-associated protein BRD2 without involvement of acetyl-lysine-binding bromodomains and recruits BRD2 to the rDNA promoter and transcribed regions via association with upstream binding factor. We show that BRD2 is required for the recruitment of the MYST-type acetyltransferase KAT7 to rDNA loci, resulting in enhanced local acetylation of histone H4. In addition, LYAR binds a complex of BRD4 and KAT7, which is then recruited to rDNA independently of the BRD2-KAT7 complex to accelerate the local acetylation of both H4 and H3. BRD2 also helps recruit BRD4 to rDNA. By contrast, LYAR has no effect on rDNA methylation or the binding of RNA polymerase I subunits to rDNA. These data suggest that LYAR promotes the association of the BRD2-KAT7 and BRD4-KAT7 complexes with transcription-competent rDNA loci but not to transcriptionally silent rDNA loci, thereby increasing rRNA synthesis by altering the local acetylation status of histone H3 and H4.

U2 - 10.1093/nar/gkz747

DO - 10.1093/nar/gkz747

M3 - Article

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JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

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