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Eur J Immunol. 2017 Aug;47(8):1317-1323. doi: 10.1002/eji.201747050. Epub 2017 Jul 14.

Revisiting the specificity of the MHC class II transactivator CIITA in classical murine dendritic cells in vivo.

Author information

1
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
2
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
3
Howard Hughes Medical Institute, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.

Abstract

Ciita was discovered for its role in regulating transcription of major histocompatibility complex class II (MHCII) genes. Subsequently, CIITA was predicted to control many other genes based on reporter and ChIP-seq analysis but few such predictions have been verified in vivo using Ciita-/- mice. Testing these predictions for classical dendritic cells (cDCs) has been particularly difficult, since Ciita-/- mice lack MHCII expression required to identify cDCs. However, recent identification of the cDC-specific transcription factor Zbtb46 allows the identification of cDCs independently of MHCII expression. We crossed Zbtb46gfp mice onto the Ciita-/- background and found that all cDC lineages developed in vivo in the absence of Ciita. We then compared the complete transcriptional profile of wild-type and Ciita-/- cDCs to define the physiological footprint of CIITA for both immature and activated cDCs. We find that CIITA exerts a highly restricted control over only the MHCII, H2-DO and H2-DM genes, in DC1 and DC2 cDC subsets, but not over other proposed targets, including Ii. These findings emphasize the caveats needed in interpreting transcription factor binding sites identified by in-vitro reporter analysis, or by ChIP-seq, which may not necessarily indicate their functional activity in vivo.

KEYWORDS:

Ciita; Dendritic cell; Transcription factor; Zbtb46

PMID:
28608405
PMCID:
PMC5757839
DOI:
10.1002/eji.201747050
[Indexed for MEDLINE]
Free PMC Article

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