Transcription Factor IRF8 Governs Enhancer 1 Landscape Dynamics in Mononuclear Phagocyte Progenitors

Posted on Posted in AMRC Research

Date: 07 Mar 2018


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 stayed resembling that of an upstream progenitor population. Our results illustrate the dynamic process by which key transcription factors regulate enhancer formation and thereby direct future gene expression to achieve mononuclear phagocyte development.


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Tomohiko TAMURA

E-mail:   Phone: +81 45 787 2616


Department of Immunology,
Yokohama City University Graduate School of Medicine

Fukuura 3-9, Kanazawa-ku, Yokohama, 236-0004 JAPAN