The pluripotency transcription factor OCT4 represses heme oxygenase-1 gene expression

FEBS Lett. 2021 Jul;595(14):1949-1961. doi: 10.1002/1873-3468.14138. Epub 2021 Jun 28.

Abstract

In embryonic stem (ES) cells, oxidative stress control is crucial for genomic stability, self-renewal, and cell differentiation. Heme oxygenase-1 (HO-1) is a key player of the antioxidant system and is also involved in stem cell differentiation and pluripotency acquisition. We found that the HO-1 gene is expressed in ES cells and induced after promoting differentiation. Moreover, downregulation of the pluripotency transcription factor (TF) OCT4 increased HO-1 mRNA levels in ES cells, and analysis of ChIP-seq public data revealed that this TF binds to the HO-1 gene locus in pluripotent cells. Finally, ectopic expression of OCT4 in heterologous systems repressed a reporter carrying the HO-1 gene promoter and the endogenous gene. Hence, this work highlights the connection between pluripotency and redox homeostasis.

Keywords: OCT4; gene modulation; heme oxygenase-1; pluripotency transcription factors; pluripotent stem cells; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Cell Differentiation / drug effects
  • Diphenylamine / analogs & derivatives
  • Diphenylamine / pharmacology
  • Embryo, Mammalian
  • Gene Expression Regulation*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Heme Oxygenase-1 / genetics*
  • Heme Oxygenase-1 / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / drug effects
  • Mouse Embryonic Stem Cells / metabolism*
  • NIH 3T3 Cells
  • Nanog Homeobox Protein / antagonists & inhibitors
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism
  • Octamer Transcription Factor-3 / antagonists & inhibitors
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / metabolism*
  • Promoter Regions, Genetic
  • Pyridines / pharmacology
  • Pyrimidines / pharmacology
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • SOXB1 Transcription Factors / antagonists & inhibitors
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction
  • Transcription, Genetic

Substances

  • Benzamides
  • Chir 99021
  • Membrane Proteins
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • Pyridines
  • Pyrimidines
  • RNA, Messenger
  • RNA, Small Interfering
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Green Fluorescent Proteins
  • mirdametinib
  • Diphenylamine
  • Luciferases
  • Heme Oxygenase-1
  • Hmox1 protein, mouse