Transcription Factor IRF8 Governs Enhancer Landscape Dynamics in Mononuclear Phagocyte Progenitors

Daisuke Kurotaki, Jun Nakabayashi, Akira Nishiyama, Haruka Sasaki, Wataru Kawase, Naofumi Kaneko, Kyoko Ochiai, Kazuhiko Igarashi, Keiko Ozato, Yutaka Suzuki, Tomohiko Tamura

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Monocytes and dendritic cells (DCs), mononuclear phagocytes essential for immune responses, develop from hematopoietic stem cells via monocyte-DC progenitors (MDPs). The molecular basis of their development remains unclear. Because promoter-distal enhancers are key to cell fate decisions, we analyzed enhancer landscapes during mononuclear phagocyte development in vivo. Monocyte- and DC-specific enhancers were gradually established at progenitor stages before the expression of associated genes. Of the transcription factors predicted to bind to these enhancers, IRF8, essential for monocyte and DC development, was found to be required for the establishment of these enhancers, particularly those common to both monocyte and DC lineages. Although Irf8 –/– mononuclear phagocyte progenitors, including MDPs, displayed grossly normal gene expression patterns, their enhancer landscapes resembled that of an upstream progenitor population. Our results illustrate the dynamic process by which key transcription factors regulate enhancer formation and, therefore, direct future gene expression to achieve mononuclear phagocyte development. The regulation of enhancer dynamics during postnatal mononuclear phagocyte development remains unclear. Kurotaki et al. analyze the enhancer landscape during monocyte and dendritic cell development in vivo. Enhancers are gradually established by transcription factors such as IRF8 at progenitor stages before the expression of associated genes, defining the progenitors’ differentiation potential.

Original languageEnglish
Pages (from-to)2628-2641
Number of pages14
JournalCell Reports
Volume22
Issue number10
DOIs
Publication statusPublished - 2018 Mar 6

Keywords

  • ChIP-seq
  • IRF8
  • dendritic cell
  • development
  • enhancer
  • monocyte
  • transcription factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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