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Akt1 mediates the posterior Hoxc gene expression through epigenetic modifications in mouse embryonic fibroblasts

Authors
 Kyoung-Ah Kong  ;  Ji-Yeon Lee  ;  Ji Hoon Oh  ;  Youra Lee  ;  Myoung Hee Kim 
Citation
 BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, Vol.1839(8) : 793-799, 2014 
Journal Title
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
ISSN
 1874-9399 
Issue Date
2014
MeSH
Amino Acid Sequence ; Animals ; Enhancer of Zeste Homolog 2 Protein ; Epigenesis, Genetic* ; Fibroblasts/metabolism ; Genes, Homeobox* ; Histone Deacetylases/physiology ; Homeodomain Proteins/genetics* ; Jumonji Domain-Containing Histone Demethylases/physiology ; Mice ; Molecular Sequence Data ; Polycomb Repressive Complex 2/physiology ; Proto-Oncogene Proteins c-akt/physiology*
Keywords
Akt1 ; Epigenetic modification ; Ezh2 ; Hdac ; Hox gene expression ; Kdm6b
Abstract
The evolutionarily conserved Hox genes are organized in clusters and expressed colinearly to specify body patterning during embryonic development. Previously, Akt1 has been identified as a putative Hox gene regulator through in silico analysis. Substantial upregulation of consecutive 5′ Hoxc genes has been observed when Akt1 is absent in mouse embryonic fibroblast (MEF) cells. In this study, we provide evidence that Akt1 regulates the 5′ Hoxc gene expression by epigenetic modifications. Enrichment of histone H3K9 acetylation and a low level of the H3K27me3 mark were detected at the posterior 5′ Hoxc loci when Akt1 is absent. A histone deacetylase (HDAC) inhibitor de-repressed 5′ Hoxc gene expression when Akt1 is present, and a DNA demethylating reagent synergistically upregulated HDAC-induced 5′ Hoxc gene expression. A knockdown study revealed that Hdac6 is mediated in the Hoxc12 repression through direct binding to the transcription start site (TSS) in the presence of Akt1. Co-immunoprecipitation analysis revealed that endogenous Akt1 directly interacted with Hdac6. Furthermore, exogenous Akt1 was enriched at the promoter region of the posterior Hoxc genes such as Hoxc11 and Hoxc12, not the Akt1-independent Hoxc5 and Hoxd10 loci. The regulation of the H3K27me3 mark by Ezh2 and Kdm6b at the 5′ Hoxc gene promoter turned out to be Akt1 dependent. Taken together, these results suggest that Akt1 mediates the posterior 5′ Hoxc gene expression through epigenetic modification such as histone methylation and acetylation, and partly through a direct binding to the promoter region of the 5′ Hoxc genes and/or Hdac6 in mouse embryonic fibroblast cells.
Full Text
http://www.sciencedirect.com/science/article/pii/S1874939914001631
DOI
10.1016/j.bbagrm.2014.06.011
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Kong, Kyoung Ah(공경아)
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, You Ra(이유라)
Lee, Ji Yeon(이지연) ORCID logo https://orcid.org/0000-0002-0670-3095
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99059
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