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Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.
Maejima, Takashi; Inoue, Tsuyoshi; Kanki, Yasuharu; Kohro, Takahide; Li, Guoliang; Ohta, Yoshihiro; Kimura, Hiroshi; Kobayashi, Mika; Taguchi, Akashi; Tsutsumi, Shuichi; Iwanari, Hiroko; Yamamoto, Shogo; Aruga, Hirofumi; Dong, Shoulian; Stevens, Junko F; Poh, Huay Mei; Yamamoto, Kazuki; Kawamura, Takeshi; Mimura, Imari; Suehiro, Jun-ichi; Sugiyama, Akira; Kaneki, Kiyomi; Shibata, Haruki; Yoshinaka, Yasunobu; Doi, Takeshi; Asanuma, Akimune; Tanabe, Sohei; Tanaka, Toshiya; Minami, Takashi; Hamakubo, Takao; Sakai, Juro; Nozaki, Naohito; Aburatani, Hiroyuki; Nangaku, Masaomi; Ruan, Xiaoan; Tanabe, Hideyuki; Ruan, Yijun; Ihara, Sigeo; Endo, Akira; Kodama, Tatsuhiko; Wada, Youichiro.
Afiliación
  • Maejima T; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan; Tokyo New Drug Research Laboratories, Kowa Company Ltd., Higashimurayama, Tokyo, Japan.
  • Inoue T; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan; Division of Nephrology and Endocrinology, The University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan.
  • Kanki Y; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Kohro T; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan; Department of Translational Research for Healthcare and Clinical Science, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
  • Li G; Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America.
  • Ohta Y; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Kimura H; Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
  • Kobayashi M; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Taguchi A; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Tsutsumi S; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Iwanari H; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Yamamoto S; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Aruga H; Thermo Fisher Scientific, South San Francisco, California, United States of America.
  • Dong S; Thermo Fisher Scientific, South San Francisco, California, United States of America.
  • Stevens JF; Thermo Fisher Scientific, South San Francisco, California, United States of America.
  • Poh HM; Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America.
  • Yamamoto K; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Kawamura T; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Mimura I; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan; Division of Nephrology and Endocrinology, The University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan.
  • Suehiro J; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Sugiyama A; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Kaneki K; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Shibata H; Tokyo New Drug Research Laboratories, Kowa Company Ltd., Higashimurayama, Tokyo, Japan.
  • Yoshinaka Y; Tokyo New Drug Research Laboratories, Kowa Company Ltd., Higashimurayama, Tokyo, Japan.
  • Doi T; Tokyo New Drug Research Laboratories, Kowa Company Ltd., Higashimurayama, Tokyo, Japan.
  • Asanuma A; Tokyo New Drug Research Laboratories, Kowa Company Ltd., Higashimurayama, Tokyo, Japan.
  • Tanabe S; Tokyo New Drug Research Laboratories, Kowa Company Ltd., Higashimurayama, Tokyo, Japan.
  • Tanaka T; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Minami T; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Hamakubo T; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Sakai J; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Nozaki N; Mab Institute Inc., North Advancement Center for Science & Technology, Sapporo, Hokkaido, Japan.
  • Aburatani H; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Nangaku M; Division of Nephrology and Endocrinology, The University of Tokyo School of Medicine, Bunkyo-ku, Tokyo, Japan.
  • Ruan X; Genome Institute of Singapore, Singapore, Singapore.
  • Tanabe H; Department of Evolutionary Studies of Biosystems, School of Advanced Sciences, The Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa, Japan.
  • Ruan Y; Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America.
  • Ihara S; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Endo A; Biopharm Research Laboratories, Inc., Koganei, Tokyo, Japan.
  • Kodama T; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
  • Wada Y; Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan; Radioisotope Center, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
PLoS One ; 9(5): e96005, 2014.
Article en En | MEDLINE | ID: mdl-24797675
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinolinas / Cromatina / Regulación de la Expresión Génica / Inhibidores de Hidroximetilglutaril-CoA Reductasas / Ensamble y Desensamble de Cromatina / Factores de Transcripción de Tipo Kruppel / Células Endoteliales de la Vena Umbilical Humana Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinolinas / Cromatina / Regulación de la Expresión Génica / Inhibidores de Hidroximetilglutaril-CoA Reductasas / Ensamble y Desensamble de Cromatina / Factores de Transcripción de Tipo Kruppel / Células Endoteliales de la Vena Umbilical Humana Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos