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GA binding protein regulates interleukin 7 receptor α-chain gene expression in T cells

Nature Immunology volume 5, pages 1036–1044 (2004)Cite this article

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Abstract

The interleukin 7 receptor α-chain (IL-7Rα) is essential for T cell development in both humans and mice and for B cell development in mice. Whereas the transcription factor PU.1 regulates IL-7Rα expression in mouse pro–B cells via a GGAA motif, we demonstrate here that GA binding protein (GABP) bound to this site and was essential in the regulation of IL-7Rα expression in T cells, where PU.1 is not expressed. Moreover, IL-7Rα expression was diminished substantially in thymocytes but was normal on B220+ fetal liver cells from mouse embryos with diminished expression of GABPα. Thus, GABP is essential for the regulation of IL-7Rα expression in T cells, and the differential regulation of IL-7Rα in distinct lymphoid lineages is achieved at least in part by differential recruitment of factors to the same GGAA motif.

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Figure 1: Identification of a DNase I–hypersensitive site and mapping of a major Il7r transcription initiation site.
Figure 2: Identification of an essential GGAA motif in the 5′ regulatory region of Il7r.
Figure 3: Identification of proteins binding to the GGAA motif in the Il7r promoter.
Figure 4: Suppression of IL-7Rα expression in T cells by siRNA targeting GABPα and GABPβ.
Figure 5: Characterization of Gabpa-trapped embryonic stem cells.
Figure 6: Diminished IL-7Rα expression in double-negative thymocytes but not B cell progenitors in Gabpatp/tp embryos.

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  • 12 September 2004

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Notes

  1. *Note: In the version of this article originally published online, some of the gene names in Figure 4 and the Figure 4 legend were incorrect. These errors have been corrected for the HTML and print versions of this article.

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Acknowledgements

We thank J. Ashwell, S. Durum, K. Jeang, H. Kim, J. Lin, A. Singer, R. Sploski, H. Young and K. Zhao (National Institutes of Health) for suggestions; K. Keyvanfar (National Institutes of Health) for help with cell sorting; K. Cui (National Institutes of Health) for help with optimization of chromatin immunoprecipitation conditions; J. Flores (National Institutes of Health) for help with timed mating of heterozygous 'Gabpa-trapped' mice; and Y. Shi (Harvard Medical School) for providing the pBS/U6 vector. Supported by National Institutes of Health (Intramural Research Training Award, 2002, R.T.).

Author information

Author notes

  1. Valentina Rovella

    Present address: Dipartimento di Medicine e Specilita' Mediche, Div. Gastroenterologia, Policlinico Via del Pozzo 71, 41100 MO, Italy

  2. Radhika Tripuraneni

    Present address: Department of General Surgery, Beth Israel Deaconess Hospital, Boston, Massachusetts, 02215, USA

Authors and Affiliations

  1. Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N252, Bethesda, 20892-1674, Maryland, USA

    Hai-Hui Xue, Julie Bollenbacher, Valentina Rovella, Radhika Tripuraneni & Warren J Leonard

  2. Transgenic Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N252, Bethesda, 20892-1674, Maryland, USA

    Yu-Bin Du & Cheng-Yu Liu

  3. Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N252, Bethesda, 20892-1674, Maryland, USA

    Ann Williams & J Philip McCoy

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Supplementary information

Supplementary Fig. 1

Specificity of antisera to GABPa and GABPb1. (JPG 91 kb)

Supplementary Fig. 2

Partially retained IL-7Ra expression of Gabpatp/tp DN thymocytes. (JPG 256 kb)

Supplementary Table 1

Target sequences for siRNA (PDF 50 kb)

Supplementary Table 2

Primers for Chromatin immunoprecipitation (PDF 57 kb)

Supplementary Table 3

Primers for RT-PCR (PDF 65 kb)

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Xue, HH., Bollenbacher, J., Rovella, V. et al. GA binding protein regulates interleukin 7 receptor α-chain gene expression in T cells. Nat Immunol 5, 1036–1044 (2004). https://doi.org/10.1038/ni1117

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