REGULATION OF C1Q AT TRANSCRIPTIONAL LEVEL

Abstract

The complement protein C1q is a large assembly from six subunits each of C1qA, C1qB and C1qC. The subunit genes are highly clustered, and any mutation in the genes can cause genetic C1q deficiency. To understand the synchronized, macrophage/dendritic cell-specific transcription of C1q genes, the three mouse C1q promoters were characterized, but only C1qb promoter displayed bona fide IFN-¿-stimulated activity. Cloning C1qb promoter at the 3¿-end supplemented 5¿ C1qa and C1qc promoter activities. The basal activity of each C1q promoter required a functional PU.1 site, and C1qb promoter depended on an EICE-ISRE overlapping element for IFN-¿ response. Ectopic PU.1 expression in non-myeloid HEK 293T cells conferred activities to C1q promoters. In BMDCs, the C1q gene locus assumed a unique conformation that brought C1q promoters into close spatial proximity, possibly contributing to the coordinated C1q gene expression in macrophage/dendritic cells. A transgenic BAC vector was constructed to generate transgenic mice.