Author:
Rico Daniel,Martens Joost HA,Downes Kate,Carrillo-de-Santa-Pau Enrique,Pancaldi Vera,Breschi Alessandra,Richardson David,Heath Simon,Saeed Sadia,Frontini Mattia,Chen Lu,Watt Stephen,Müller Fabian,Clarke Laura,Kerstens Hindrik HD,Wilder Steven P,Palumbo Emilio,Djebali Sarah,Raineri Emanuele,Merkel Angelika,Esteve-Codina Anna,Sultan Marc,van Bommel Alena,Gut Marta,Yaspo Marie-Laure,Rubio Miriam,Fernandez José María,Attwood Anthony,de la Torre Victor,Royo Romina,Fragkogianni Stamatina,Gelpí Josep Lluis,Torrents David,Iotchkova Valentina,Logie Colin,Aghajanirefah Ali,Singh Abhishek A,Janssen-Megens Eva M,Berentsen Kim,Erber Wendy,Rendon Augusto,Kostadima Myrto,Loos Remco,van der Ent Martijn A,Kaan Anita,Sharifi Nilofar,Paul Dirk S,Ifrim Daniela C,Quintin Jessica,Love Michael I.,Pisano David G,Burden Frances,Foad Nicola,Farrow Samantha,Zerbino Daniel R,Dunham Ian,Kuijpers Tacow,Lehrach Hans,Lengauer Thomas,Bertone Paul,Netea Mihai G,Vingron Martin,Beck Stephan,Flicek Paul,Gut Ivo,Ouwehand Willem H,Bock Christoph,Soranzo Nicole,Guigo Rodericw,Valencia Alfonso,Stunnenberg Hendrik G
Abstract
ABSTRACTNeutrophils 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.
Publisher
Cold Spring Harbor Laboratory