PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H1 receptor

Histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis, and its expression level strongly correlates with the severity of symptoms. However, the mechanism underlying this remains unknown. Here we report the mechanism of H1R gene up-regulation. The luciferase assay reveal...

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Published inScientific reports Vol. 2; no. 1; p. 916
Main Authors Mizuguchi, Hiroyuki, Miyagi, Kohei, Terao, Takuma, Sakamoto, Noriko, Yamawaki, Yosuke, Adachi, Tsubasa, Ono, Shohei, Sasaki, Yohei, Yoshimura, Yoshiyuki, Kitamura, Yoshiaki, Takeda, Noriaki, Fukui, Hiroyuki
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 03.12.2012
Subjects
Allergic rhinitis
Deoxyribonucleic acid
DNA
Gene expression
Gene regulation
Histamine
Poly(ADP-ribose) polymerase
Protein kinase C
Regulatory sequences
Signal transduction
Transcription factors
Up-regulation
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Abstract Histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis, and its expression level strongly correlates with the severity of symptoms. However, the mechanism underlying this remains unknown. Here we report the mechanism of H1R gene up-regulation. The luciferase assay revealed the existence of two promoter regions, A and B1. Two AP-1 and one Ets-1 bound to region A, while Ku86, Ku70, and PARP-1 bound to region B1. Ku86 was responsible for DNA binding and poly(ADP-ribosyl)ated in response to phorbol-12-myristate-13-acetate stimulation, inducing its dissociation from region B1 that is crucial for promoter activity. Knockdown of Ku86 gene enhanced up-regulation of H1R gene expression. Experiments using inhibitors for MEK and PARP-1 indicate that regions A and B1 are downstream regulatory elements of the PKCδ/ERK/PARP-1 signaling pathway. Data suggest a novel mechanism for the up-regulation of H1R gene expression.
AbstractList Histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis, and its expression level strongly correlates with the severity of symptoms. However, the mechanism underlying this remains unknown. Here we report the mechanism of H1R gene up-regulation. The luciferase assay revealed the existence of two promoter regions, A and B1. Two AP-1 and one Ets-1 bound to region A, while Ku86, Ku70, and PARP-1 bound to region B1. Ku86 was responsible for DNA binding and poly(ADP-ribosyl)ated in response to phorbol-12-myristate-13-acetate stimulation, inducing its dissociation from region B1 that is crucial for promoter activity. Knockdown of Ku86 gene enhanced up-regulation of H1R gene expression. Experiments using inhibitors for MEK and PARP-1 indicate that regions A and B1 are downstream regulatory elements of the PKCδ/ERK/PARP-1 signaling pathway. Data suggest a novel mechanism for the up-regulation of H1R gene expression.
Histamine H 1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis, and its expression level strongly correlates with the severity of symptoms. However, the mechanism underlying this remains unknown. Here we report the mechanism of H1R gene up-regulation. The luciferase assay revealed the existence of two promoter regions, A and B1. Two AP-1 and one Ets-1 bound to region A, while Ku86, Ku70, and PARP-1 bound to region B1. Ku86 was responsible for DNA binding and poly(ADP-ribosyl)ated in response to phorbol-12-myristate-13-acetate stimulation, inducing its dissociation from region B1 that is crucial for promoter activity. Knockdown of Ku86 gene enhanced up-regulation of H1R gene expression. Experiments using inhibitors for MEK and PARP-1 indicate that regions A and B1 are downstream regulatory elements of the PKCδ/ERK/PARP-1 signaling pathway. Data suggest a novel mechanism for the up-regulation of H1R gene expression.
ArticleNumber 916
Author Adachi, Tsubasa
Sasaki, Yohei
Mizuguchi, Hiroyuki
Yamawaki, Yosuke
Takeda, Noriaki
Miyagi, Kohei
Fukui, Hiroyuki
Terao, Takuma
Sakamoto, Noriko
Yoshimura, Yoshiyuki
Kitamura, Yoshiaki
Ono, Shohei
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Snippet Histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis, and its expression level strongly correlates with the severity of...
Histamine H 1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis, and its expression level strongly correlates with the severity of...
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SourceType Open Access Repository
Aggregation Database
StartPage 916
SubjectTerms Allergic rhinitis
Deoxyribonucleic acid
DNA
Gene expression
Gene regulation
Histamine
Poly(ADP-ribose) polymerase
Protein kinase C
Regulatory sequences
Signal transduction
Transcription factors
Up-regulation
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Title PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H1 receptor
URI https://www.proquest.com/docview/1897400817/abstract/
https://pubmed.ncbi.nlm.nih.gov/PMC3512088
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