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

• 来源期刊: 生物化学与生物物理学报（英文版）
• 关键词: Hox genes Akt1 HAT Gcn5
• 年，卷（期）: 2017,（7）
• 页码范围: 643-648
• 页数: 6页
• 语种: 英文
• DOI: 10.1093/abbs/gmx051

摘要

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 Hoxgenes.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,theHoxc11 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 Gcn5knockdown 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 Hoxc1 1 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.