UNDERSTANDING THE TRANSCRIPTIONAL CONTROL OF COMPLEMENT PROTEIN C1Q

Abstract

C1q is a serum complement protein present that plays an important role in modulating the host immune system. C1q is assembled from three subunits coded by independent genes located as a cluster (C1qA-C1qC-C1qB) and are specifically expressed in macrophages and DCs. We observed that the three C1q genes were expressed in a synchronized manner at both basal and IFN¿-induced levels. A 53-bp element in the C1qB promoter was identified as the putative IFN¿-responsive element that coordinately regulates the C1q gene cluster. PU.1 and IRF8 were shown to bind to the 53-bp element directly but STAT1 regulates C1qB promoter through regulating IRF8 expression. The C1q gene cluster is conserved across species, but the mode of responses to IFN¿ vary. Collectively, our results reveal a novel transcriptional mechanism that synchronizes C1q gene expression and provide a genomic template for understanding synchronized transcription in gene clusters.