1: J Immunol. 2004 Aug 15;173(4):2552-61. 

Transcriptional regulation of the human TLR9 gene.

Takeshita F, Suzuki K, Sasaki S, Ishii N, Klinman DM, Ishii KJ.

Section of Retroviral Immunology, Center for Biologics Evaluation and Research,
Food and Drug Administration, Bethesda, MD 20892, USA.
takesita@yokohama-cu.ac.jp

To clarify the molecular basis of human TLR9 (hTLR9) gene expression, the
activity of the hTLR9 gene promoter was characterized using the human myeloma
cell line RPMI 8226. Reporter gene analysis and EMSA demonstrated that hTLR9
gene transcription was regulated via four cis-acting elements, cAMP response
element, 5'-PU box, 3'-PU box, and a C/EBP site, that interacted with the CREB1,
Ets2, Elf1, Elk1, and C/EBPalpha transcription factors. Other members of the
C/EBP family, such as C/EBPbeta, C/EBPdelta, and C/EBPepsilon, were also
important for TLR9 gene transcription. CpG DNA-mediated suppression of TLR9 gene
transcription led to decreased binding of the trans-acting factors to their
corresponding cis-acting elements. It appeared that suppression was mediated via
c-Jun and NF-kappaB p65 and that cooperation among CREB1, Ets2, Elf1, Elk1, and
C/EBPalpha culminated in maximal transcription of the TLR9 gene. These findings
will help to elucidate the mechanism of TLR9 gene regulation and to provide
insight into the process by which TLR9 evolved in the mammalian immune system.

PMID: 15294971 [PubMed - indexed for MEDLINE]


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