Jmjd3 contributes to the control of gene expression in LPS-activated macrophages

Francesca De Santa, Vipin Narang, Zhei Hwee Yap, Betsabeh Khoramian Tusi, Thomas Burgold, Liv Austenaa, Gabriele Bucci, Marieta Caganova, Samuele Notarbartolo, Stefano Casola, Giuseppe Testa, Wing Kin Sung, Chia Lin Wei, Gioacchino Natoli

Research output: Contribution to journalArticlepeer-review

Abstract

Jmjd3, a JmjC family histone demethylase, is induced by the transcription factor NF-kB in response to microbial stimuli. Jmjd3 erases H3K27me3, a histone mark associated with transcriptional repression and involved in lineage determination. However, the specific contribution of Jmjd3 induction and H3K27me3 demethylation to inflammatory gene expression remains unknown. Using chromatin immunoprecipitation-sequencing we found that Jmjd3 is preferentially recruited to transcription start sites characterized by high levels of H3K4me3, a marker of gene activity, and RNA polymerase II (Pol-II). Moreover, 70% of lipopolysaccharide (LPS)-inducible genes were found to be Jmjd3 targets. Although most Jmjd3 target genes were unaffected by its deletion, a few hundred genes, including inducible inflammatory genes, showed moderately impaired Pol-II recruitment and transcription. Importantly, most Jmjd3 target genes were not associated with detectable levels of H3K27me3, and transcriptional effects of Jmjd3 absence in the window of time analysed were uncoupled from measurable effects on this histone mark. These data show that Jmjd3 fine-tunes the transcriptional output of LPS-activated macrophages in an H3K27 demethylation-independent manner.

Original languageEnglish
Pages (from-to)3341-3352
Number of pages12
JournalEMBO Journal
Volume28
Issue number21
DOIs
Publication statusPublished - Nov 2009

Keywords

  • Histone demethylase
  • JmjC
  • Macrophages
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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