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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