Histone methyltransferase DOT1L differentially affects the development of dendritic cell subsets
Rianne G Bouma, Willem-Jan de Leeuw, Aru Z Wang, Muddassir Malik, Joeke GC Stolwijk, Veronique AL Konijn, Anne Mensink, Natalie Proost, Maarten K Nijen Twilhaar, Tibor van Welsem, Negisa Seyed Toutounchi, Alsya J Affandi, Jip T van Dinter, Fred van Leeuwen, Joke MM den Haan
TL;DR
DOT1L, an epigenetic enzyme, influences the development of different types of dendritic cells and affects their immune functions.
Contribution
This study reveals the differential role of DOT1L in regulating canonical dendritic cell subsets through its methyltransferase activity.
Findings
DOT1L deletion reduces myeloid progenitors and increases cDC2s, while cDC1s remain unaffected.
In vitro deletion of Dot1l leads to loss of pDCs and reduced IFNα production.
DOT1L inhibition suppresses antigen presentation pathways in dendritic cells.
Abstract
The epigenetic writer DOT1L guides the development of dendritic cells through its catalytic activity, differentially affecting canonical dendritic cell subsets. Dendritic cells (DCs) orchestrate immune responses. Their development is controlled by transcription factors, but epigenetic mechanisms remain poorly understood. DOT1L emerges as a key epigenetic regulator in immune cells. Mapping DOT1L-mediated histone H3K79 methylation in canonical DC subsets revealed that DOT1L modified common and DC subset–specific genes. Deletion of Dot1l in vivo or in vitro decreased myeloid progenitors and increased cDC2s, whereas cDC1s remained unchanged. In addition, in vitro deletion of Dot1l led to loss of plasmacytoid DCs (pDCs) and of IFNα production upon stimulation. Upon in vivo deletion, a decrease in pDCs was only observed after subsequent in vitro expansion. This difference was likely related…
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Taxonomy
TopicsImmunotherapy and Immune Responses · Epigenetics and DNA Methylation · Genomics and Chromatin Dynamics