Rapid Downregulation of H3K4me3 Binding to Immunoregulatory Genes in Altered Gravity in Primary Human M1 Macrophages.

Autor: Vahlensieck C; Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Thiel CS; Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.; Department of Machine Design, Engineering Design and Product Development, Institute of Mechanical Engineering, Otto-von-Guericke-University Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany.; Space Life Sciences Laboratory (SLSL), Kennedy Space Center, 505 Odyssey Way, Exploration Park, Merritt Island, FL 32953, USA.; UZH Space Hub, Air Force Center, Air Base Dübendorf, Überlandstrasse 270, 8600 Dubendorf, Switzerland., Christoffel S; Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Herbst S; Ernst-Abbe-Hochschule (EAH) Jena, Department of Industrial Engineering, Carl-Zeiss-Promenade 2, 07745 Jena, Germany., Polzer J; Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Lauber BA; Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Wolter S; Ernst-Abbe-Hochschule (EAH) Jena, Department of Industrial Engineering, Carl-Zeiss-Promenade 2, 07745 Jena, Germany., Layer LE; Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Hinkelbein J; Department for Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, 50937 Cologne, Germany., Tauber S; Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland., Ullrich O; Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.; Department of Machine Design, Engineering Design and Product Development, Institute of Mechanical Engineering, Otto-von-Guericke-University Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany.; Space Life Sciences Laboratory (SLSL), Kennedy Space Center, 505 Odyssey Way, Exploration Park, Merritt Island, FL 32953, USA.; UZH Space Hub, Air Force Center, Air Base Dübendorf, Überlandstrasse 270, 8600 Dubendorf, Switzerland.; Ernst-Abbe-Hochschule (EAH) Jena, Department of Industrial Engineering, Carl-Zeiss-Promenade 2, 07745 Jena, Germany.; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Dec 29; Vol. 24 (1). Date of Electronic Publication: 2022 Dec 29.
DOI: 10.3390/ijms24010603
Abstrakt: The sensitivity of human immune system cells to gravity changes has been investigated in numerous studies. Human macrophages mediate innate and thus rapid immune defense on the one hand and activate T- and B-cell-based adaptive immune response on the other hand. In this process they finally act as immunoeffector cells, and are essential for tissue regeneration and remodeling. Recently, we demonstrated in the human Jurkat T cell line that genes are differentially regulated in cluster structures under altered gravity. In order to study an in vivo near system of immunologically relevant human cells under physically real microgravity, we performed parabolic flight experiments with primary human M1 macrophages under highly standardized conditions and performed chromatin immunoprecipitation DNA sequencing (ChIP-Seq) for whole-genome epigenetic detection of the DNA-binding loci of the main transcription complex RNA polymerase II and the transcription-associated epigenetic chromatin modification H3K4me3. We identified an overall downregulation of H3K4me3 binding loci in altered gravity, which were unequally distributed inter- and intrachromosomally throughout the genome. Three-quarters of all affected loci were located on the p arm of the chromosomes chr5, chr6, chr9, and chr19. The genomic distribution of the downregulated H3K4me3 loci corresponds to a substantial extent to immunoregulatory genes. In microgravity, analysis of RNA polymerase II binding showed increased binding to multiple loci at coding sequences but decreased binding to central noncoding regions. Detection of altered DNA binding of RNA polymerase II provided direct evidence that gravity changes can lead to altered transcription. Based on this study, we hypothesize that the rapid transcriptional response to changing gravitational forces is specifically encoded in the epigenetic organization of chromatin.
Databáze: MEDLINE
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