The role of Complement Factor H Regulation in the CNS
The complement system is an important component of innate immunity that requires proper regulation to avoid inappropriate activation. This regulation is provided for by many proteins, such as complement Factor H (CFH), a secreted regulator of the alternative pathway that aids in the cleavage of C3b protein. Despite its regulatory function, gene and promoter polymorphisms of CFH have been implicated in disease of many patients with age-related macular degeneration and atypical hemolytic uremic syndrome, indicating that a better understanding of this gene’s regulation is valuable. Presently, little work has been done to address the role of CFH in the central nervous system (CNS). We have cloned the murine CFH promoter and have made truncation constructs to examine CFH gene regulation in cells of the CNS. Our studies show that CFH mRNA is present in CNS cell types, and that specific regions throughout the promoter contain possible enhancers and repressors. Database mining of these regions indicates that there are potential transcription factor binding sites conserved between many different species, which led us to investigate specific transcription factor binding interactions in these regions. Through these studies we hope to elucidate the transcriptional regulation of CFH in the CNS.
Fraczek LA, Martin CB, Martin BK. c-Jun and c-Fos regulate the complement factor H promoter in murine astrocytes. Mol Immunol. 2011 Sep 13. [Epub ahead of print] PubMed PMID: 21920606.
Fraczek LA, Martin BK. Transcriptional control of genes for soluble complement cascade regulatory proteins. Mol Immunol. 2010 Nov-Dec;48(1-3):9-13. Epub 2010 Sep 25. Review. PubMed PMID: 20869772.