The Histone Demethylase KDM5 Activates Gene Expression by Recognizing Chromatin Context through Its PHD Reader Motif

Xingyin Liu, Julie Secombe

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

KDM5 family proteins are critically important transcriptional regulators whose physiological functions in the context of a whole animal remain largely unknown. Using genome-wide gene expression and binding analyses in Drosophila adults, we demonstrate that KDM5 (Lid) is a direct regulator of genes required for mitochondrial structure and function. Significantly, this occurs independently of KDM5's well-described JmjC domain-encoded histone demethylase activity. Instead, it requires the PHD motif of KDM5 that binds to histone H3 that is di- or trimethylated on lysine 4 (H3K4me2/3). Genome-wide, KDM5 binding overlaps with the active chromatin mark H3K4me3, and a fly strain specifically lacking H3K4me2/3 binding shows defective KDM5 promoter recruitment and gene activation. KDM5 therefore plays a central role in regulating mitochondrial function by utilizing its ability to recognize specific chromatin contexts. Importantly, KDM5-mediated regulation of mitochondrial activity is likely to be key in human diseases caused by dysfunction of this family of proteins.

Original languageEnglish (US)
Pages (from-to)2219-2231
Number of pages13
JournalCell Reports
Volume13
Issue number10
DOIs
StatePublished - Jan 1 2015

Keywords

  • H3K4me3
  • KDM5
  • Lid
  • PHD motif
  • histone
  • mitochondria
  • transcription

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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