Regulation of macrophage IFNγ-stimulated gene expression by the transcriptional coregulator CITED1

Subramani, A.; Hite, M.; Garcia, S.; Maxwell, J.; Kondee, H.; Millican, G.; McClelland, Erin E.; Seipelt-Thiemann, R.; Nelson, D.

doi:10.1242/jcs.260529

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Regulation of macrophage IFNγ-stimulated gene expression by the transcriptional coregulator CITED1

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MLA citation style (9th ed.)

Subramani, A, et al. Regulation of Macrophage Ifnγ-stimulated Gene Expression by the Transcriptional Coregulator Cited1. The Company of Biologists. 2023. marian.hykucommons.org/concern/generic_works/bc762b05-9aff-4bef-9899-ec3c0d81c413.

APA citation style (7th ed.)

S. A, H. M, G. S, M. J, K. H, M. G, M. E. E, S. R, & N. D. (2023). Regulation of macrophage IFNγ-stimulated gene expression by the transcriptional coregulator CITED1. https://marian.hykucommons.org/concern/generic_works/bc762b05-9aff-4bef-9899-ec3c0d81c413

Chicago citation style (CMOS 17, author-date)

Subramani, A., Hite, M., Garcia, S., Maxwell, J., Kondee, H., Millican, G., McClelland, Erin E. et al. Regulation of Macrophage Ifnγ-Stimulated Gene Expression by the Transcriptional Coregulator Cited1. The Company of Biologists. 2023. https://marian.hykucommons.org/concern/generic_works/bc762b05-9aff-4bef-9899-ec3c0d81c413.

Note: These citations are programmatically generated and may be incomplete.

Macrophages serve as a first line of defense against microbial pathogens. Exposure to interferon-γ (IFNγ) increases interferon-stimulated gene (ISG) expression in these cells, resulting in enhanced antimicrobial and proinflammatory activity. Although this response must be sufficiently vigorous to ensure the successful clearance of pathogens, it must also be carefully regulated to prevent tissue damage. This is controlled in part by CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2), a transcriptional coregulator that limits ISG expression by inhibiting STAT1 and IRF1. Here, we show that the closely related Cited1 is an ISG, which is expressed in a STAT1-dependent manner, and that IFNγ stimulates the nuclear accumulation of CITED1 protein. In contrast to CITED2, ectopic CITED1 enhanced the expression of a subset of ISGs, including Ccl2, Ifit3b, Isg15 and Oas2. This effect was reversed in a Cited1-null cell line produced by CRISPR-based genomic editing. Collectively, these data show that CITED1 maintains proinflammatory gene expression during periods of prolonged IFNγ exposure and suggest that there is an antagonistic relationship between CITED proteins in the regulation of macrophage inflammatory function.

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