2. Academic Validation
  3. Histone H3Y99sulf regulates hepatocellular carcinoma responding to hypoxia

Histone H3Y99sulf regulates hepatocellular carcinoma responding to hypoxia

  • J Biol Chem. 2024 Feb 2:105721. doi: 10.1016/j.jbc.2024.105721.
Sibi Yin 1,  Weixing Yu 2,  Runxin Zhou 1,  Xiao Zeng 1,  Li Jiang 3,  Yu Wang 1,  Dingyuan Guo 1,  Fuqiang Tong 1,  Leya He 4,  Jun Zhao 5,  Yugang Wang 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
  • 2 Department of Biochemistry and Molecular Biology, College of Basic Medicine, Jining Medical University, Jining, 272067, China.
  • 3 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China, 430060; Department of Neurology, The Affiliated Nanhua Hospital, University of South China, Hengyang, 421001, China.
  • 4 Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 5 Department of Anatomy, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Cell Architecture Research Center, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
  • 6 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Cell Architecture Research Center, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address: yugangw@hust.edu.cn.
PMID: 38311175 DOI: 10.1016/j.jbc.2024.105721
Abstract

Histone H3 Tyr-99 sulfation (H3Y99sulf) is a recently identified histone mark that can cross-talk with H4R3me2a to regulate gene transcription, but its role in Cancer biology is less studied. Here we report that H3Y99sulf is a cancer-associated histone mark that can mediate hepatocellular carcinoma (HCC) cells responding to hypoxia. Hypoxia-stimulated Snail pathway elevates the expression of PAPSS2, which serves as a source of PAPS for histone sulfation and results in upregulation of H3Y99sulf. The transcription factor TDRD3 is the downstream effector of H3Y99sulf-H4R3me2a axis in HCC. It reads and co-localizes with the H3Y99sulf-H4R3me2a dual mark in the promoter regions of HIF1A and PDK1 to regulate gene transcription. Depletion of SULT1B1 can effectively reduce the occurrence of H3Y99sulf-H4R3me2a-TDRD3 axis in gene promoter regions and lead to downregulation of targeted gene transcription. HIF-1α and PDK1 are master regulators for hypoxic responses and Cancer metabolism. Disruption of the H3Y99sulf-H4R3me2a-TDRD3 axis can inhibit the expression and functions of HIF-1α and PDK1, resulting in suppressed proliferation, tumor growth, and survival of HCC cells suffering hypoxia stress. The present study extends the regulatory and functional mechanisms of H3Y99sulf and improves our understanding of its role in Cancer biology.

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