Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription

Ubieta K, Garcia M, Groetsch B, Uebe S, Stein M, Ekici AB, Schett G, Mielenz D, Bozec A, Weber G (2017)


Publication Type: Journal article

Publication year: 2017

Journal

DOI: 10.1084/jem.20160514

Abstract

The role of AP-1 transcription factors in early B cell development and function is still incompletely characterized. Here we address the role of Fra-2 in B cell differentiation. Deletion of Fra-2 leads to impaired B cell proliferation in the bone marrow. In addition, IL-7-stimulated pro-B cell cultures revealed a reduced differentiation from large pre-B cells to small B cells and immature B cells. Gene profiling and chromatin immunoprecipitation sequencing analyses unraveled a transcriptional reduction of the transcription factors Foxo1, Irf4, Ikaros, and Aiolos in Fra-2-deficient B cells. Moreover, expression of IL7R? and Rag 1/2, downstream targets of Irf4 and Foxo1, were also reduced in the absence of Fra-2. Pro-B cell proliferation and small pre-B cell differentiation were fully rescued by expression of Foxo1 and Irf4 in Fra-2-deficient pro-B cells. Hence, Fra-2 is a key upstream regulator of Foxo1 and Irf4 expression and influences proliferation and differentiation of B cells at multiple stages.

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APA:

Ubieta, K., Garcia, M., Groetsch, B., Uebe, S., Stein, M., Ekici, A.B.,... Weber, G. (2017). Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription. Journal of Experimental Medicine. https://dx.doi.org/10.1084/jem.20160514

MLA:

Ubieta, Kenia, et al. "Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription." Journal of Experimental Medicine (2017).

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