Transcription factor PU.1
cis-regulatory region sequence-specific DNA binding
PU.1 plays a pivotal role in dendritic cell migration from the periphery to secondary lymphoid organs <i>via</i> regulating CCR7 expression.
C-C chemokine receptor type 7 (CCR7) is essential for migration of dendritic cells (DCs) to draining lymph nodes. PU.1/<i>Spi1</i> is a transcription factor playing a critical role in the gene regulation of DCs. PU.1 knockdown decreased the expression of CCR7 in bone marrow-derived DCs and subsequently attenuated migration <i>in vitro</i> and <i>in vivo</i>. Reporter assays, EMSA, and chromatin immunoprecipitation assays revealed that PU.1 binds to the most proximal Ets motif of the <i>Ccr7</i> promoter, which is involved in transcriptional activation. The CCR7 expression level, which was higher in the programmed cell death 1 ligand 2 (PD-L2)<sup>+</sup> population than in the PD-L2<sup>-</sup> population and was markedly suppressed by TGF-β treatment, coincided with the binding level of PU.1 to the <i>Ccr7</i> promoter. The PU.1 binding level in CCR7<sup>high</sup> mesenteric lymph nodes DCs was higher than in other DC subtypes. The involvement of PU.1 in the expression of the <i>CCR7</i> gene was also observed in human DCs. We conclude that PU.1 plays a pivotal role in DC migration by transactivating the <i>CCR7</i> gene <i>via</i> the Ets motif in the promoter in both humans and mice.-Yashiro, T., Takeuchi, H., Nakamura, S., Tanabe, A., Hara, M., Uchida, K., Okumura, K., Kasakura, K., Nishiyama, C. PU.1 plays a pivotal role in dendritic cell migration from the periphery to secondary lymphoid organs <i>via</i> regulating CCR7 expression.