@article{oai:ir.soken.ac.jp:00005454,
 author = {MAEJIMA, Takashi and INOUE, Tsuyoshi and KANKI, Yasuharu and KOHRO, Takahide and LI, Guoliang and OHTA, Yoshihiro and KIMURA, Hiroshi and KOBAYASHI, Mika and TAGUCHI, Akashi and TSUTSUMI, Shuichi and IWANARI, Hiroko and YAMAMOTO, Shogo and ARUGA, Hirofumi and DONG, Shoulian and STEVENS, Junko F and POH, Huay Mei and YAMAMOTO, Kazuki and KAWAMURA, Takeshi and MIMURA, Imari and SUEHIRO, Jun-ichi and SUGIYAMA, Akira and KANEKI, Kiyomi and SHIBATA, Haruki and YOSHINAKA, Yasunobu and DOI, Takeshi and ASANUMA, Akimune and TANABE, Sohei and TANAKA, Toshiya and MINAMI, Takashi and HAMAKUBO, Takao and SAKAI, Juro and NOZAKI, Naohito and ABURATANI, Hiroyuki and NANGAKU, Masaomi and RUAN, Xiaoan and TANABE, Hideyuki and RUAN, Yijun and IHARA, Sigeo and ENDO, Akira and KODAMA, Tatsuhiko and WADA, Youichiro},
 issue = {5},
 journal = {PLoS One, PLoS One},
 month = {May},
 note = {Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells.},
 title = {Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.},
 volume = {9},
 year = {2014}
}