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Direct Evidence for Pitavastatin Induced Chromatin Structure Change in the KLF4 Gene in Endothelial Cells

Overview of attention for article published in PLOS ONE, May 2014
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Title
Direct Evidence for Pitavastatin Induced Chromatin Structure Change in the KLF4 Gene in Endothelial Cells
Published in
PLOS ONE, May 2014
DOI 10.1371/journal.pone.0096005
Pubmed ID
Authors

Takashi Maejima, Tsuyoshi Inoue, Yasuharu Kanki, Takahide Kohro, Guoliang Li, Yoshihiro Ohta, Hiroshi Kimura, Mika Kobayashi, Akashi Taguchi, Shuichi Tsutsumi, Hiroko Iwanari, Shogo Yamamoto, Hirofumi Aruga, Shoulian Dong, Junko F. Stevens, Huay Mei Poh, Kazuki Yamamoto, Takeshi Kawamura, Imari Mimura, Jun-ichi Suehiro, Akira Sugiyama, Kiyomi Kaneki, Haruki Shibata, Yasunobu Yoshinaka, Takeshi Doi, Akimune Asanuma, Sohei Tanabe, Toshiya Tanaka, Takashi Minami, Takao Hamakubo, Juro Sakai, Naohito Nozaki, Hiroyuki Aburatani, Masaomi Nangaku, Xiaoan Ruan, Hideyuki Tanabe, Yijun Ruan, Sigeo Ihara, Akira Endo, Tatsuhiko Kodama, Youichiro Wada

Abstract

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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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Japan 2 4%
Unknown 48 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 24%
Researcher 11 22%
Student > Master 3 6%
Professor 3 6%
Student > Bachelor 2 4%
Other 9 18%
Unknown 10 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 32%
Agricultural and Biological Sciences 14 28%
Medicine and Dentistry 5 10%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Mathematics 1 2%
Other 4 8%
Unknown 9 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 May 2014.
All research outputs
#18,371,959
of 22,755,127 outputs
Outputs from PLOS ONE
#154,400
of 194,177 outputs
Outputs of similar age
#164,177
of 227,397 outputs
Outputs of similar age from PLOS ONE
#3,560
of 4,758 outputs
Altmetric has tracked 22,755,127 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 194,177 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.1. This one is in the 10th percentile – i.e., 10% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 227,397 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 4,758 others from the same source and published within six weeks on either side of this one. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.