Comparative analysis of neutrophil and monocyte epigenomes
| Autor: | Rubio M, van Bommel A, Nilofar Sharifi, Alessandra Breschi, David G. Pisano, David J. Richardson, Paul Bertone, Marie-Laure Yaspo, Stephen B. Watt, Emanuele Raineri, de la Torre, Hinri Kerstens, Angelika Merkel, Pancaldi, Gelpí Jl, Emilio Palumbo, Martin Vingron, van der Ent Ma, Joost H.A. Martens, Royo R, Daniel R. Zerbino, Myrto Kostadima, Ian Dunham, Augusto Rendon, Laura Clarke, Sadia Saeed, Gut I, S. Farrow, Dirk S. Paul, Ali Aghajanirefah, Enrique Carrillo-de-Santa-Pau, Valencia A, Love Mi, Kuijpers T, Marc Sultan, Frances Burden, Anna Esteve-Codina, Nicola Foad, Jessica Quintin, Steven P. Wilder, Iotchkova, Remco Loos, Daniela C. Ifrim, Stephan Beck, Simon Heath, Henk Stunnenberg, Daniel Rico, Lu Chen, Roderic Guigó, Torrents D, Kim Berentsen, Gut M, Fernandez Jm, Abhishek Singh, Paul Flicek, Willem H. Ouwehand, Mihai G. Netea, Hans Lehrach, Thomas Lengauer, Kate Downes, Erber W, Christoph Bock, Stamatina Fragkogianni, Franz-Josef Müller, Sarah Djebali, Colin Logie, Anita Kaan, Eva M. Janssen-Megens, Mattia Frontini, Nicole Soranzo, Antony P. Attwood |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0303 health sciences
Innate immune system Cellular differentiation Monocyte Epigenome Biology 3. Good health Cell biology Chromatin 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis DNA methylation medicine Epigenetics 030304 developmental biology Epigenomics |
| DOI: | 10.1101/237784 |
| Popis: | Neutrophils and monocytes provide a first line of defense against infections as part of the innate immune system. Here we report the integrated analysis of transcriptomic and epigenetic landscapes for circulating monocytes and neutrophils with the aim to enable downstream interpretation and functional validation of key regulatory elements in health and disease. We collected RNA-seq data, ChIP-seq of six histone modifications and of DNA methylation by bisulfite sequencing at base pair resolution from up to 6 individuals per cell type. Chromatin segmentation analyses suggested that monocytes have a higher number of cell-specific enhancer regions (4-fold) compared to neutrophils. This highly plastic epigenome is likely indicative of the greater differentiation potential of monocytes into macrophages, dendritic cells and osteoclasts. In contrast, most of the neutrophil-specific features tend to be characterized by repressed chromatin, reflective of their status as terminally differentiated cells. Enhancers were the regions where most of differences in DNA methylation between cells were observed, with monocyte-specific enhancers being generally hypomethylated. Monocytes show a substantially higher gene expression levels than neutrophils, in line with epigenomic analysis revealing that gene more active elements in monocytes. Our analyses suggest that the overexpression of c-Myc in monocytes and its binding to monocyte-specific enhancers could be an important contributor to these differences. Altogether, our study provides a comprehensive epigenetic chart of chromatin states in primary human neutrophils and monocytes, thus providing a valuable resource for studying the regulation of the human innate immune system. |
| Databáze: | OpenAIRE |
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