Adult neovascularization relies on the recruitment of circulating cells, but their angiogenic roles and recruitment mechanisms are unclear. We examined expression of anigiogenic genes of primary endothelial cells and pericytes, derived from human brain cortex. Among the genes involved in angiogenesis, we found that stromal cell-derived factor-1 (SDF-1) is exclusively expressed in pericytes and its receptor (CXCR4) exists in endothelial cells. SDF-1 is a CXC chemokine that binds and signals through the CXCR4 receptor, playing an essential role in embryonic B lymphopoiesis, myelopoiesis and organogenesis. Moreover, recent works suggest important roles for SDF-1 in metastasis progression and diabetic retinopathy. To understand the molecular mechanism that regulates cell type-specific SDF-1 expression, we have cloned and functionally analysed its 5' flanking regulatory region. Analysis of deletion mutants of SDF-1 promoter revealed that basal promoter activity resides in -100 bp upstream of the transcription initiation site. Among the predicted binding sites in the -100 bp, site-directed mutagenesis showed that an Sp-1 binding site is critical for the promoter activity. Transfected SDF-1 promoter construct was active in endothelial cells that do not express endogeneous SDF-1 transcript. Treatment of DNA methyltransferase inhibitor (5-azacytidine) or HDAC inhibitor (trichostatin A) induced transcription of SDF-1 in endothelial cells. In conclusion, pericyte-specific expression of SDF-1 is regulated by epigenetic mechanism rather than tissue-specific transcription factors.