Epigenetic program and transcription factor circuitry of dendritic cell development

Qiong Lin, Heike Chauvistre, Ivan G. Costa, Eduardo G. Gusmao, Saskia Mitzka, Sonja Haenzelmann, Bianka Baying, Theresa Klisch, Richard Moriggl, Benoit Hennuy, Hubert Smeets, Kurt Hoffmann, Vladimir Benes, Kristin Sere, Martin Zenke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

36 Citations (Web of Science)

Abstract

Dendritic cells (DC) are professional antigen presenting cells that develop from hematopoietic stem cells through successive steps of lineage commitment and differentiation. Multipotent progenitors (MPP) are committed to DC restricted common DC progenitors (CDP), which differentiate into specific DC subsets, classical DC (cDC) and plasmacytoid DC (pDC). To determine epigenetic states and regulatory circuitries during DC differentiation, we measured consecutive changes of genome-wide gene expression, histone modification and transcription factor occupancy during the sequel MPP-CDP-cDC/pDC. Specific histone marks in CDP reveal a DC-primed epigenetic signature, which is maintained and reinforced during DC differentiation. Epigenetic marks and transcription factor PU.1 occupancy increasingly coincide upon DC differentiation. By integrating PU.1 occupancy and gene expression we devised a transcription factor regulatory circuitry for DC commitment and subset specification. The circuitry provides the transcription factor hierarchy that drives the sequel MPP-CDP-cDC/pDC, including Irf4, Irf8, Tcf4, Spib and Stat factors. The circuitry also includes feedback loops inferred for individual or multiple factors, which stabilize distinct stages of DC development and DC subsets. In summary, here we describe the basic regulatory circuitry of transcription factors that drives DC development.
Original languageEnglish
Pages (from-to)9680-9693
JournalNucleic Acids Research
Volume43
Issue number20
DOIs
Publication statusPublished - 16 Nov 2015

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