Journal article
Analysis of Interleukin-21-Induced Prdm1 Gene Regulation Reveals Functional Cooperation of STAT3 and IRF4 Transcription Factors
H Kwon, D Thierry-Mieg, J Thierry-Mieg, HP Kim, J Oh, C Tunyaplin, S Carotta, CE Donovan, ML Goldman, P Tailor, K Ozato, DE Levy, SL Nutt, K Calame, WJ Leonard
Immunity | CELL PRESS | Published : 2009
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 I..
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Awarded by National Heart, Lung, and Blood Institute
Funding Acknowledgements
We thank H C Morse III for NFS201 and NFS202 cells, D E Schones for valuable discussions and assistance with handling the Illumina raw ChIP-Seq data and for processing ChIP-Seq data, K Cui and T -Y Roh for help with Solexa sequencing, the NHLBI Affymetrix Core and N Raghavachan, X Xu, and D Liu for help with generating, analyzing. and handling Affymetrix data, and J -X Lin, H Young, K Zhao, and K -T Jeang for valuable discussions and/or critical comments. This work was supported by the Division of Intramural Research, National Heart, Lung. and Blood Institute, and by the National Center for Biotechnology Information, National Library of Medicine W J L is an inventor on patents and patent applications related to IL-21