This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bu, P.
Right arrow Articles by Dent, S. Y. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bu, P.
Right arrow Articles by Dent, S. Y. R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2007, p. 3405-3416, Vol. 27, No. 9
0270-7306/07/$08.00+0     doi:10.1128/MCB.00066-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Loss of Gcn5 Acetyltransferase Activity Leads to Neural Tube Closure Defects and Exencephaly in Mouse Embryos{triangledown}

Ping Bu,1 Yvonne A. Evrard,2,{dagger} Guillermina Lozano,2,3 and Sharon Y. R. Dent1,2*

Department of Biochemistry and Molecular Biology,1 Program in Genes and Development,2 Department of Cancer Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 770303

Received 12 January 2007/ Returned for modification 1 February 2007/ Accepted 14 February 2007

Gcn5 was the first transcription-related histone acetyltransferase (HAT) to be identified. However, the functions of this enzyme in mammalian cells remain poorly defined. Deletion of Gcn5 in mice leads to early embryonic lethality with increased apoptosis in mesodermal lineages. Here we show that deletion of p53 allows Gcn5–/– embryos to survive longer, but Gcn5–/– p53–/– embryos still die in midgestation. Interestingly, embryos homozygous for point mutations in the Gcn5 catalytic domain survive significantly longer than Gcn5–/– or Gcn5–/– p53–/– mice. In contrast to Gcn5–/– embryos, Gcn5hat/hat embryos do not exhibit increased apoptosis but do exhibit severe cranial neural tube closure defects and exencephaly. Together, our results indicate that Gcn5 has important, HAT-independent functions in early development and that Gcn5 acetyltransferase activity is required for cranial neural tube closure in the mouse.

* Corresponding author (previously known as Sharon Y. Roth). Mailing address: Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Unit 1000, Houston, TX 77030. Phone: (713) 834-6269. Fax: (713) 834-6273. E-mail: sroth{at}mdanderson.org

{triangledown} Published ahead of print on 26 February 2007.

{dagger} Present address: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.

Molecular and Cellular Biology, May 2007, p. 3405-3416, Vol. 27, No. 9
0270-7306/07/$08.00+0     doi:10.1128/MCB.00066-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mao, X., Gluck, N., Li, D., Maine, G. N., Li, H., Zaidi, I. W., Repaka, A., Mayo, M. W., Burstein, E. (2009). GCN5 is a required cofactor for a ubiquitin ligase that targets NF-{kappa}B/RelA. Genes Dev. 23: 849-861 [Abstract] [Full Text]  
  • Gamper, A. M., Kim, J., Roeder, R. G. (2009). The STAGA Subunit ADA2b Is an Important Regulator of Human GCN5 Catalysis. Mol. Cell. Biol. 29: 266-280 [Abstract] [Full Text]  
  • Wang, Y.-L., Faiola, F., Xu, M., Pan, S., Martinez, E. (2008). Human ATAC Is a GCN5/PCAF-containing Acetylase Complex with a Novel NC2-like Histone Fold Module That Interacts with the TATA-binding Protein. J. Biol. Chem. 283: 33808-33815 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»