Hypoxia-inducible factor 1 recruits FACT and RNF20/40 to mediate histone ubiquitination and transcriptional activation of target genes

Yajing Lyu; Yongkang Yang; Varen Talwar; Haiquan Lu; Chelsey Chen; Shaima Salman; Elizabeth E. Wicks; Tina Yi-Ting Huang; Daiana Drehmer; Yufeng Wang; Qiaozhu Zuo; Emmanuel Datan; Walter Jackson, III; Dominic Dordai; Ru Wang; Gregg L. Semenza

Cell Reports (Apr 2024)

Hypoxia-inducible factor 1 recruits FACT and RNF20/40 to mediate histone ubiquitination and transcriptional activation of target genes

Yajing Lyu,
Yongkang Yang,
Varen Talwar,
Haiquan Lu,
Chelsey Chen,
Shaima Salman,
Elizabeth E. Wicks,
Tina Yi-Ting Huang,
Daiana Drehmer,
Yufeng Wang,
Qiaozhu Zuo,
Emmanuel Datan,
Walter Jackson, III,
Dominic Dordai,
Ru Wang,
Gregg L. Semenza

Affiliations

Yajing Lyu: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Yongkang Yang: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA
Varen Talwar: Johns Hopkins University, Baltimore, MD 21218, USA
Haiquan Lu: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA
Chelsey Chen: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Shaima Salman: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Elizabeth E. Wicks: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Tina Yi-Ting Huang: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Daiana Drehmer: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Yufeng Wang: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Qiaozhu Zuo: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Emmanuel Datan: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Walter Jackson, III: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Dominic Dordai: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Ru Wang: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Gregg L. Semenza: Armstrong Oxygen Biology Research Center and Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 4
p. 113972

Abstract

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Summary: Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates cellular adaptation to decreased oxygen availability. HIF-1 recruits chromatin-modifying enzymes leading to changes in histone acetylation, citrullination, and methylation at target genes. Here, we demonstrate that hypoxia-inducible gene expression in estrogen receptor (ER)-positive MCF7 and ER-negative SUM159 human breast cancer cells requires the histone H2A/H2B chaperone facilitates chromatin transcription (FACT) and the H2B ubiquitin ligase RING finger protein 20/40 (RNF20/40). Knockdown of FACT or RNF20/40 expression leads to decreased transcription initiation and elongation at HIF-1 target genes. Mechanistically, FACT and RNF20/40 are recruited to hypoxia response elements (HREs) by HIF-1 and stabilize binding of HIF-1 (and each other) at HREs. Hypoxia induces the monoubiquitination of histone H2B at lysine 120 at HIF-1 target genes in an HIF-1-dependent manner. Together, these findings delineate a cooperative molecular mechanism by which FACT and RNF20/40 stabilize multiprotein complex formation at HREs and mediate histone ubiquitination to facilitate HIF-1 transcriptional activity.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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