The Lysine Acetyltransferase GCN5 Is Required for iNKT Cell Development through EGR2 Acetylation

Yajun Wang, Chawon Yun, Beixue Gao, Yuanming Xu, Yana Zhang, Yiming Wang, Qingfei Kong, Fang Zhao, Chyung Ru Wang, Sharon Y.R. Dent, Jian Wang, Xiangping Xu*, Hua Bin Li, Deyu Fang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner. At the molecular level, GCN5 is a specific lysine acetyltransferase of early growth responsive gene 2 (EGR2), a transcription factor required for iNKT cell development. GCN5-mediated acetylation positively regulated EGR2 transcriptional activity, and both genetic and pharmacological GCN5 suppression specifically inhibited the transcription of EGR2 target genes in iNKT cells, including Runx1, promyelocytic leukemia zinc finger protein (PLZF), interleukin (IL)-2Rb, and T-bet. Therefore, our study revealed GCN5-mediated EGR2 acetylation as a molecular mechanism that regulates iNKT development.

Original languageEnglish (US)
Pages (from-to)600-612
Number of pages13
JournalCell reports
Volume20
Issue number3
DOIs
StatePublished - Jul 18 2017

Keywords

  • EGR2
  • GCN5
  • acetylation
  • iNKT

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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