The ETS Factor Myeloid Elf-1-Like Factor (MEF)/Elf4 Is Transcriptionally and Functionally Activated by Hypoxia

• Suico Mary Ann

  Department of Molecular Medicine, Faculty of Pharmaceutical Sciences, Kumamoto University

• Taura Manabu

  Division of Hematopoiesis, Center for AIDS Research, Kumamoto University

• Kudo Eriko

  Division of Hematopoiesis, Center for AIDS Research, Kumamoto University

• Gotoh Kumiko

  Division of Hematopoiesis, Center for AIDS Research, Kumamoto University

• Shuto Tsuyoshi

  Department of Molecular Medicine, Faculty of Pharmaceutical Sciences, Kumamoto University

• Okada Seiji

  Division of Hematopoiesis, Center for AIDS Research, Kumamoto University

• Kai Hirofumi

  Department of Molecular Medicine, Faculty of Pharmaceutical Sciences, Kumamoto University

Abstract

Hypoxia-inducible factor (HIF)-1α is a transcription factor belonging to the HIF family that is activated in mammalian cells during conditions of low oxygen tension or hypoxia to induce an adaptive response and promote cell survival. Some of the genes targeted by HIF-1α are important for angiogenesis and proliferation. Here, we found that the E26 transformation-specific (ETS) transcription factor myeloid elf-1-like factor (MEF)/Elf4 is activated by HIF-1α. MEF induces genes such as human beta-defensin 2 (HβD2) and perforin (PRF1), and is known to affect the cell cycle. Treatment with hypoxia mimetic CoCl₂ or low O₂ incubation up-regulated MEF mRNA and protein levels in various cell lines. HIF-1α overexpression in HEK293 cells also increased MEF mRNA and protein levels. In contrast, HIF-1α knockdown by small interfering RNA (siRNA) suppressed the induction of MEF in response to hypoxia. HIF-1α binds to the hypoxia response element in the MEF promoter region (−200 bp) and activates MEF promoter under hypoxia condition. The induction of MEF by hypoxia/HIF-1α correlated with the increase of MEF target genes HβD2 and PRF1. Intriguingly, the hypoxia-induced expression of HIF-1α target gene vascular endothelial growth factor (VEGF) was enhanced by the exogenous addition of MEF. Overall, these data indicate that hypoxia or HIF-1α positively regulates MEF expression and function.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 39 (4), 641-647, 2016

  The Pharmaceutical Society of Japan

Keywords

• myeloid elf-1-like factor
• hypoxia inducible factor-1α
• transcription
• vascular endothelial growth factor
• hypoxia
• E26 transformation-specific (ETS) transcription factor

Details

• CRID: 1390282679608475136
• NII Article ID: 130005141679
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b15-00796
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 027221276
• PubMed: 27040637
• Web Site: http://id.ndl.go.jp/bib/027221276
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027221276
• Web Site: https://www.jstage.jst.go.jp/article/bpb/39/4/39_b15-00796/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016362782
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed