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ACL and HAT1 form a nuclear module to acetylate histone H4K5 and promote cell proliferation

Author

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  • Qiutao Xu

    (Huazhong Agricultural University)

  • Yaping Yue

    (Huazhong Agricultural University)

  • Biao Liu

    (Huazhong Agricultural University)

  • Zhengting Chen

    (Huazhong Agricultural University)

  • Xuan Ma

    (Huazhong Agricultural University)

  • Jing Wang

    (Huazhong Agricultural University)

  • Yu Zhao

    (Huazhong Agricultural University)

  • Dao-Xiu Zhou

    (Huazhong Agricultural University
    University Paris-Saclay)

Abstract

Acetyl-CoA utilized by histone acetyltransferases (HAT) for chromatin modification is mainly generated by ATP-citrate lyase (ACL) from glucose sources. How ACL locally establishes acetyl-CoA production for histone acetylation remains unclear. Here we show that ACL subunit A2 (ACLA2) is present in nuclear condensates, is required for nuclear acetyl-CoA accumulation and acetylation of specific histone lysine residues, and interacts with Histone AcetylTransferase1 (HAT1) in rice. The rice HAT1 acetylates histone H4K5 and H4K16 and its activity on H4K5 requires ACLA2. Mutations of rice ACLA2 and HAT1 (HAG704) genes impair cell division in developing endosperm, result in decreases of H4K5 acetylation at largely the same genomic regions, affect the expression of similar sets of genes, and lead to cell cycle S phase stagnation in the endosperm dividing nuclei. These results indicate that the HAT1-ACLA2 module selectively promotes histone lysine acetylation in specific genomic regions and unravel a mechanism of local acetyl-CoA production which couples energy metabolism with cell division.

Suggested Citation

  • Qiutao Xu & Yaping Yue & Biao Liu & Zhengting Chen & Xuan Ma & Jing Wang & Yu Zhao & Dao-Xiu Zhou, 2023. "ACL and HAT1 form a nuclear module to acetylate histone H4K5 and promote cell proliferation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39101-4
    DOI: 10.1038/s41467-023-39101-4
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    1. Caryn S. Ross-Innes & Rory Stark & Andrew E. Teschendorff & Kelly A. Holmes & H. Raza Ali & Mark J. Dunning & Gordon D. Brown & Ondrej Gojis & Ian O. Ellis & Andrew R. Green & Simak Ali & Suet-Feung C, 2012. "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer," Nature, Nature, vol. 481(7381), pages 389-393, January.
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