Differential expression of stromal cell-derived factor 1 in human brain microvascular endothelial cells and pericytes involves histone modifications.
Stromal cell-derived factor 1 (SDF-1) regulates neovascularization, which is coordinately controlled by endothelial cells (EC) and their surrounding cells, pericytes or smooth muscle cells. In the basal state, SDF-1 expression is much lower in EC than in their surrounding cells. In this study, we evaluated epigenetic regulation to determine if it is involved in the mechanism responsible for the differential expression of SDF-1 in two types of vascular cells, brain microvascular EC (HBMEC) and pericytes (HBMP). We found that HBMEC did not express SDF-1, but that HBMP did. Furthermore, treatment of EC with 5-aza-2'-dexoycytidine and trichostatin A resulted in a remarkable restoration of SDF-1 expression. Additionally, bisulfite-sequencing analysis revealed no differences in the methylation state of SDF-1 promoter between HBMEC and HBMP. Finally, a chromatin immunoprecipitation assay revealed reduced levels of histone H3 lysine 9 (H3K9) acetylation and H3K4 trimethylation with concomitant enhancement of H3K9 trimethylation in HBMEC relative to HBMP, which suggests that histone modifications are involved in the cell-specific expression of SDF-1.
Seo
Jungwon
J
Department of Molecular Medicine, Ewha Womans University Medical School, 911-1 Mok 6-dong, Yangchun-gu, Seoul 158-710, South Korea.
Kim
Yong-Ou
YO
Jo
Inho
I
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000166:cytology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics*; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D015870:Gene Expression; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020286:Pericytes / Q000378:metabolism*; D011401:Promoter Regions, Genetic
D054377:Chemokine CXCL12; D002843:Chromatin; D006657:Histones; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine