Analysis of Interleukin-21-Induced Prdm1 Gene Regulation Reveals Functional Cooperation of STAT3 and IRF4 Transcription Factors
- Author(s)
- Kwon, H; Thierry-Mieg, D; Thierry-Mieg, J; Kim, HP; Oh, J; Tunyaplin, C; Carotta, S; Donovan, CE; Goldman, ML; Tailor, P; Ozato, K; Levy, DE; Nutt, SL; Calame, K; Leonard, WJ;
- Details
- Publication Year 2009-12-18,Volume 31,Issue #6,Page 941-952
- Journal Title
- IMMUNITY
- Publication Type
- Journal Article
- Abstract
- Interleukin-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 lrf4(-/-) mice showed impaired IL-21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4.
- Publisher
- CELL PRESS
- Keywords
- PLASMA-CELL DIFFERENTIATION; REPRESSOR BLIMP-1; IL-2 RECEPTOR; B-LYMPHOCYTES; FAMILY; CHAIN; IMMUNODEFICIENCY; HOMEOSTASIS; MODULATION; EXPRESSION
- Publisher's Version
- https://doi.org/10.1016/j.immuni.2009.10.008
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- Refer to copyright notice on published article.
Creation Date: 2009-12-18 12:00:00