Blimp-1/PRDM1 mediates transcriptional suppression of the NLR gene NLRP12/Monarch-1. Academic Article uri icon

abstract

  • 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.

published proceedings

  • J Immunol

altmetric score

  • 3

author list (cited authors)

  • Lord, C. A., Savitsky, D., Sitcheran, R., Calame, K., Wright, J. R., Ting, J., & Williams, K. L.

citation count

  • 24

complete list of authors

  • Lord, Christopher A||Savitsky, David||Sitcheran, Raquel||Calame, Kathryn||Wright, Jo Rae||Ting, Jenny Pan-Yun||Williams, Kristi L

publication date

  • March 2009