TY - JOUR
T1 - Differential expression of stromal cell-derived factor 1 in human brain microvascular endothelial cells and pericytes involves histone modifications
AU - Seo, Jungwon
AU - Kim, Yong Ou
AU - Jo, Inho
N1 - Funding Information:
This work was supported in part by the Korean Food and Drug Administration grant (08512KFDA418) and the Korea National Institute of Health intramural research grant (348-6111-213-000-207).
PY - 2009/5/8
Y1 - 2009/5/8
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Endothelial cells
KW - Epigenetic
KW - Histone modifications
KW - Pericytes
KW - Stromal cell-derived factor 1
UR - http://www.scopus.com/inward/record.url?scp=64049109279&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.03.049
DO - 10.1016/j.bbrc.2009.03.049
M3 - Article
C2 - 19289100
AN - SCOPUS:64049109279
VL - 382
SP - 519
EP - 524
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -