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The histone acetylation mediated by Gcn5 regulates the Hoxc11 gene expression in MEFs

Authors
 Ji Hoon Oh  ;  Ji-Yeon Lee  ;  Kyoung-Ah Kong  ;  Jie Min Kim  ;  Myoung Hee Kim 
Citation
 ACTA BIOCHIMICA ET BIOPHYSICA SINICA, Vol.49(7) : 643-648, 2017 
Journal Title
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
ISSN
 1672-9145 
Issue Date
2017
Keywords
Akt1 ; Gcn5 ; HAT ; Hox genes
Abstract
Hox genes are responsible for encoding transcription factors that are essential for anterior-posterior body patterning at early stages of embryogenesis. However, detailed mechanisms of Hox genes are yet to be defined. Protein kinase B alpha (Akt1) was previously identified as a possible upstream regulator of Hox genes. Furthermore, the Hoxc11 gene has been upregulated in Akt1 null (Akt1-/-) mouse embryonic fibroblasts (MEFs), while repressed in wild-type MEFs. In this study, we propose to investigate the role of Gcn5, a histone acetyltransferase, in the regulation of Hoxc11 expression in MEFs. We showed that the H3 lysine 9 acetylation (H3K9ac) status has the same correlation with Hoxc11 expression and reported that Gcn5 is associated with the upregulation of Hoxc11 expression through H3K9ac in Akt1-/- MEFs. Since Hoxc11 was upregulated through histone acetylation in Akt1-/- MEFs, a functional role of Gcn5 on Hoxc11 expression was analyzed in Akt1-/- MEFs treated with Gcn5 specific inhibitor or transfected with Gcn5-small interfering RNA (Gcn5-siRNA). When the expression of Hoxc11 was analyzed using RT-PCR and real-time PCR, the Hoxc11 mRNA level was found to be similar in both Akt1-/- MEFs and control-siRNA transfected Akt1-/- MEFs. However, the Hoxc11 expression level was decreased in Gcn5-inhibited or Gcn5-knockdown Akt1-/- MEFs. Additionally, to analyze Gcn5-mediated histone acetylation status, chromatin immunoprecipitation assay was carried out in Gcn5-siRNA-transfected Akt1-/- MEFs. The H3K9ac at the Hoxc11 locus was decreased in Gcn5-knockdown Akt1-/- MEFs compared to controls. Based on these findings, we conclude that Gcn5 regulates Hoxc11 gene expression through mediating site-specific H3K9 acetylation in Akt1-/- MEFs.
Full Text
https://academic.oup.com/abbs/article-lookup/doi/10.1093/abbs/gmx051
DOI
10.1093/abbs/gmx051
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Hee(김명희) ORCID logo https://orcid.org/0000-0001-5652-1452
Oh, Ji Hoon(오지훈) ORCID logo https://orcid.org/0000-0001-6619-5515
Lee, Ji Yeon(이지연) ORCID logo https://orcid.org/0000-0002-0670-3095
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154293
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