1. JMJD3 regulates [CD4.sup.+] T cell trafficking by targeting actin cytoskeleton regulatory gene Pdlim4
- Author
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Fu, Chuntang, Li, Qingtian, Zou, Jia, Xing, Changsheng, Luo, Mei, Yin, Bingnan, Chu, Junjun, Yu, Jiaming, Liu, Xin, Wang, Helen Y., and Wang, Rong-Fu
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Actin -- Analysis ,Genes -- Analysis ,Transcription (Genetics) -- Analysis ,DNA binding proteins -- Analysis ,T cells -- Analysis ,Biochemistry ,Criminal investigation ,Phosphates ,Sphingosine ,Cell differentiation ,Gene expression ,Health care industry - Abstract
Histone H3K27 demethylase JMJD3 plays a critical role in gene expression and T cell differentiation. However, the role and mechanisms of JMJD3 in T cell trafficking remain poorly understood. Here, we show that JMJD3 deficiency in [CD4.sup.+] T cells resulted in an accumulation of T cells in the thymus and reduction of T cell number in the secondary lymphoid organs. We identified PDLIM4 as a significantly downregulated target gene in JMJD3- deficient [CD4.sup.+] T cells by gene profiling and ChIP-Seq analyses. We further showed that PDLIM4 functioned as an adaptor protein to interact with sphingosine-1 phosphate receptor 1 (S1P1) and filamentous actin (F-actin), thus serving as a key regulator of T cell trafficking. Mechanistically, JMJD3 bound to the promoter and gene-body regions of the Pdlim4 gene and regulated its expression by interacting with zinc finger transcription factor KLF2. Our findings have identified Pdlim4 as a JMJD3 target gene that affects T cell trafficking by cooperating with S1P1 and have provided insights into the molecular mechanisms by which JMJD3 regulates genes involved in T cell trafficking., Introduction T cell development in the thymus is a multistep process. Early thymic progenitor cells (TPCs) differentiate into T cell receptor-expressing (TCR-expressing) [CD4.sup.+][CD8.sup.+] double-positive (DP) thymocytes in the cortex and [...]
- Published
- 2019
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