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Common distal elements orchestrate CIITA isoform-specific expression in multiple cell types

Genes & Immunity volume 15, pages 543–555 (2014)Cite this article

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Abstract

Major histocompatibility class II (MHC-II) expression is critical for immune responses and is controlled by the MHC-II transactivator CIITA. CIITA is primarily regulated at the transcriptional level and is expressed from three main promoters with myeloid, lymphoid and interferon (IFN)-γ-treated non-hematopoietic cells using promoters pI, pIII and pIV, respectively. Recent studies in non-hematopoietic cells suggest that a series of distal regulatory elements may be involved in regulating CIITA transcription. To identify distal elements in B cells, a DNase I hypersensitivity screen was performed, revealing a series of potential novel regulatory elements. These elements were analyzed computationally and biochemically. Several regions displayed active histone modifications and/or enhanced expression of a reporter gene. Four of the elements interacted with pIII in B cells. These same four regions were also found to interact with pI in splenic dendritic cells (spDC). Intriguingly, examination of the above interactions in pI-knockout-derived spDC showed a switch to the next available promoter, pIII. Extensive DNA methylation was found at the pI region in B cells, suggesting that this promoter is not accessible in B cells. Thus, CIITA expression is likely mediated in hematopoietic cells by common elements with promoter accessibility having a part in promoter choice.

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Acknowledgements

We thank the members of the Boss lab for their helpful critiques and suggestions. This work was supported by the National Institutes of Health grants RO1GM47310 and T32GM0008490.

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Author notes

  1. J W Austin

    Present address: 2Current address: Integrative Immunobiology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.,

  2. W M Zinzow-Kramer

    Present address: 3Current address: Department of Psychology, Emory University, Atlanta, GA 30322, USA.,

Authors and Affiliations

  1. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA

    S Lohsen, P Majumder, C D Scharer, B G Barwick, J W Austin, W M Zinzow-Kramer & J M Boss

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Correspondence to J M Boss.

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Lohsen, S., Majumder, P., Scharer, C. et al. Common distal elements orchestrate CIITA isoform-specific expression in multiple cell types. Genes Immun 15, 543–555 (2014). https://doi.org/10.1038/gene.2014.49

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