التفاصيل البيبلوغرافية
| العنوان: |
Repression of Ccr9 Transcription in Mouse T Lymphocyte Progenitors by the Notch Signaling Pathway. |
| المؤلفون: |
Krishnamoorthy, Veena1, Carr, Tiffany2, de Pooter, Renee F.2, Akinola, Emanuelle Olumide2, Gounari, Fotini2,3, Kee, Barbara L.1,2,4 bkee@bsd.uchicago.edu |
| المصدر: |
Journal of Immunology. 4/1/2015, Vol. 194 Issue 7, p3191-3200. 10p. |
| مصطلحات موضوعية: |
*CHEMOKINE receptors, *GENETIC transcription, *T cells, *CELL growth, *THYMOCYTES, *DOWNREGULATION, *TRANSCRIPTION factors, *RNA polymerase II |
| مستخلص: |
The chemokine receptor CCR9 controls the immigration of multipotent hematopoietic progenitor cells into the thymus to sustain T cell development. Postimmigration, thymocytes downregulate CCR9 and migrate toward the subcapsular zone where they recombine their TCR β-chain and γ-chain gene loci. CCR9 is subsequently upregulated and participates in the localization of thymocytes during their selection for self-tolerant receptor specificities. Although the dynamic regulation of CCR9 is essential for early T cell development, the mechanisms controlling CCR9 expression have not been determined. In this article, we show that key regulators of T cell development, Notchl and the E protein transcription factors E2A and HEB, coordinately control the expression of Ccr9. E2A and HEB bind at two putative enhancers upstream of Ccr9 and positively regulate CCR9 expression at multiple stages of T cell development. In contrast, the canonical Notch signaling pathway prevents the recruitment of p300 to the putative Ccr9 enhancers, resulting in decreased acetylation of histone H3 and a failure to recruit RNA polymerase II to the Ccr9 promoter. Although Notch signaling modestly modulates the binding of E proteins to one of the two Ccr9 enhancers, we found that Notch signaling represses Ccr9 in T cell lymphoma lines in which Ccr9 transcription is independent of E protein function. Our data support the hypothesis that activation of Notchl has a dominant-negative effect on Ccr9 transcription and that Notchl and E proteins control the dynamic expression of Ccr9 during T cell development. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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