title: The DNA-binding factor Ctcf critically controls gene expression in macrophages.
abstract: Macrophages play an important role in immunity and homeostasis. Upon pathogen recognition via specific receptors, they rapidly induce inflammatory responses. This process is tightly controlled at the transcriptional level. The DNA binding zinc-finger protein CCCTC-binding factor (Ctcf) is a crucial regulator of long-range chromatin interactions and coordinates specific communication between transcription factors and gene expression processes. In this study, the Ctcf gene was specifically deleted in myeloid cells by making use of the transgenic Cre-LoxP system. Conditional deletion of the Ctcf gene in myeloid cells induced a mild phenotype in vivo. Ctcf-deficient mice exhibited significantly reduced expression of major histocompatibility complex (MHC) class II in the liver. Ctcf-deficient macrophages demonstrated a normal surface phenotype and phagocytosis capacity. Upon Toll-like receptor (TLR) stimulation, they produced normal levels of the pro-inflammatory cytokines IL-12 and IL-6, but manifested a strongly impaired capacity to produce tumor-necrosis factor (TNF) and IL-10, as well as to express the IL-10 family members IL-19, IL-20 and IL-24. Taken together, our data demonstrate a role of Ctcf that involves fine-tuning of macrophage function.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Nikolic
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Dowty
authors.initials: D
authors.lastname: Movita
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Margaretha E H
authors.initials: ME
authors.lastname: Lambers
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ribeiro de Almeida
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Paula
authors.initials: P
authors.lastname: Biesta
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Kreefft
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Marjolein J W
authors.initials: MJ
authors.lastname: de Bruijn
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bergen
authors.affiliation: Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: Galjart
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Andre
authors.initials: A
authors.lastname: Boonstra
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Rudi
authors.initials: R
authors.lastname: Hendriks
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000076246:CCCTC-Binding Factor; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007124:Immunoenzyme Techniques; D019426:Integrases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008285:Major Histocompatibility Complex / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012097:Repressor Proteins; D051193:Toll-Like Receptors; C045073:Cre recombinase; D019426:Integrases