The transcription factor reservoir and chromatin landscape in activated plasmacytoid dendritic cells

Abstract

Transcription factors (TFs) control gene expression by direct binding to regulatory regions of target genes but also by impacting chromatin landscapes and thereby modulating DNA accessibility for other TFs. To date, the global TF reservoir in plasmacytoid dendritic cells (pDCs), a cell type with the unique capacity to produce unmatched amounts of type I interferons, has not been fully characterized. To fill this gap, we have performed a comprehensive analysis in naïve and TLR9-activated pDCs in a time course study covering early timepoints after stimulation (2h, 6h, 12h) integrating gene expression (RNA-Seq), chromatin landscape (ATAC-Seq) and Gene Ontology studies. We found that 70% of all described TFs are expressed in pDCs for at least one stimulation time point and that activation predominantly "turned on" the chromatin regions associated with TF genes. We hereby define the complete set of TLR9-regulated TFs in pDCs. Further, this study identifies the AP-1 family of TFs as potentially important but so far less well characterized regulators of pDC function.

Advances in understanding epigenetic impacts on dendritic cell regulation and function

“…performed ATAC‐seq on cells derived and purified from bone marrow. Following preparation of the ATAC‐seq libraries, sequencing and bioinformatics analysis was performed where a genomic signal map was created through simulation, ATAC‐seq peaks were identified and false reads were removed 25 . Hence, the study discovered the pool of TFs and chromatin environment in activated pDCs.…”

“…A study by Mann-Nüttel et al identified several TFs which exhibited binding reactivity with DNA as well as a significant epigenetic modulation. 25 The study identified the entire set of TFs in pDCs which are regulated by TLR9, and the significance of a family of TFs called AP-1 (activator protein 1). In this direction, Mann-Nüttel et al performed ATAC-seq on cells derived and purified from bone marrow.…”