Cell Reports
Volume 22, Issue 10, 6 March 2018, Pages 2628-2641
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Article
Transcription Factor IRF8 Governs Enhancer Landscape Dynamics in Mononuclear Phagocyte Progenitors

https://doi.org/10.1016/j.celrep.2018.02.048Get rights and content
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Highlights

  • Enhancer dynamics during mononuclear phagocyte development are deciphered

  • Transcription factors regulating the enhancers are depicted

  • IRF8 is essential for the establishment of enhancers at progenitor stages

Summary

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.

Keywords

monocyte
dendritic cell
development
transcription factor
enhancer
ChIP-seq
IRF8

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