| First Author | Lord CA | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 5 | Pages | 2948-58 |
| PubMed ID | 19234190 | Mgi Jnum | J:146247 |
| Mgi Id | MGI:3837085 | Doi | 10.4049/jimmunol.0801692 |
| Citation | Lord CA, et al. (2009) Blimp-1/PRDM1 mediates transcriptional suppression of the NLR gene NLRP12/Monarch-1. J Immunol 182(5):2948-58 |
| abstractText | NLR (nucleotide-binding domain, leucine-rich repeat) proteins are intracellular regulators of host defense and immunity. One NLR gene, NLRP12 (NLR family, pyrin domain containing 12)/Monarch-1, has emerged as an important inhibitor of inflammatory gene expression in human myeloid cells. This is supported by genetic analysis linking the loss of a functional NLRP12 protein to hereditary periodic fever. NLRP12 transcription is diminished by specific TLR stimulation and myeloid cell maturation, consistent with its role as a negative regulator of inflammation. The NLRP12 promoter contains a novel Blimp-1 (B lymphocyte-induced maturation protein-1)/PRDM1 (PR domain-containing 1, with ZNF domain) binding site, and Blimp-1 reduces NLRP12 promoter activity, expression, and histone 3 acetylation. Blimp-1 associates with the endogenous NLRP12 promoter in a TLR-inducible manner and mediates the down-regulation of NLRP12 expression by TLR agonists. As expected, the expression of NLRP12 and Blimp-1 is inversely correlated. Analysis of Blimp-1(-/-) murine myeloid cells provides physiologic evidence that Blimp-1 reduces NLRP12 gene expression during cell differentiation. This demonstrates a novel role for Blimp-1 in the regulation of an NLR gene. |
