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The DNA-binding factor Ctcf critically controls gene expression in macrophages

Cellular & Molecular Immunology volume 11, pages 58–70 (2014)Cite this article

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.

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Acknowledgements

We would like to thank Frank Sleutels, Ralph Stadhouders and Anthonie Groothuismink (Erasmus MC Rotterdam) for assistance at various stages of the project. This work was supported by VENI grant no. 91666067 from the Netherlands Organisation for Scientific Research.

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Author notes

  1. Tatjana Nikolic

    Present address: Current address: Dr T Nikolic, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands,

  2. Claudia Ribeiro de Almeida: Dr CR de Almeida, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

  3. Tatjana Nikolic and Dowty Movita: Both authors contributed equally.

  4. Andre Boonstra and Rudi Hendriks: Both authors contributed equally.

Authors and Affiliations

  1. Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands

    Tatjana Nikolic, Margaretha EH Lambers, Claudia Ribeiro de Almeida, Marjolein JW de Bruijn, Ingrid Bergen & Rudi Hendriks

  2. Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands

    Dowty Movita, Paula Biesta, Kim Kreefft & Andre Boonstra

  3. Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands

    Niels Galjart

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Nikolic, T., Movita, D., Lambers, M. et al. The DNA-binding factor Ctcf critically controls gene expression in macrophages. Cell Mol Immunol 11, 58–70 (2014). https://doi.org/10.1038/cmi.2013.41

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