کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3353786 1216889 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Analysis of Interleukin-21-Induced Prdm1 Gene Regulation Reveals Functional Cooperation of STAT3 and IRF4 Transcription Factors
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Analysis of Interleukin-21-Induced Prdm1 Gene Regulation Reveals Functional Cooperation of STAT3 and IRF4 Transcription Factors
چکیده انگلیسی

SummaryInterleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo and furthermore revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4−/− T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4−/− mice showed impaired IL-21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 31, Issue 6, 18 December 2009, Pages 941–952
نویسندگان
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