Loss of Gcn5l2 leads to increased apoptosis and mesodermal defects during mouse development (original) (raw)

Nature Genetics volume 26, pages 229–232 (2000)Cite this article

Abstract

Histone acetyltransferases regulate transcription, but little is known about the role of these enzymes in developmental processes. Gcn5 (encoded by Gcn5l2) and Pcaf, mouse histone acetyltransferases, share similar sequences and enzymatic activities1. Both interact with p300 and CBP (encoded by Ep300 and Crebbp, respectively), two other histone acetyltransferases that integrate multiple signalling pathways1. Pcaf is thought to participate in many of the cellular processes regulated by p300/CBP (refs 2–8), but the functions of Gcn5 are unknown in mammalian cells. Here we show that the gene Pcaf is dispensable in mice. In contrast, _Gcn5l2_-null embryos die during embryogenesis. These embryos develop normally to 7.5 days post coitum (d.p.c.), but their growth is severely retarded by 8.5 d.p.c. and they fail to form dorsal mesoderm lineages, including chordamesoderm and paraxial mesoderm. Differentiation of extra-embryonic and cardiac mesoderm seems to be unaffected. Loss of the dorsal mesoderm lineages is due to a high incidence of apoptosis in the Gcn5l2 mutants that begins before the onset of morphological abnormality. Embryos null for both Gcn5l2 and Pcaf show even more severe defects, indicating that these histone acetyltransferases have overlapping functions during embryogenesis. Our studies are the first to demonstrate that specific acetyltransferases are required for cell survival and mesoderm formation during mammalian development.

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Acknowledgements

This work was supported by grants from the USARMC and the Robert A. Welch Foundation to S.Y.R. and a grant from the NIH to R.R.B.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Texas-M.D. Anderson Cancer Center, Houston, Texas, USA
    Wanting Xu, Diane G. Edmondson, Yvonne A. Evrard & Sharon Y. Roth
  2. Department of Molecular Genetics, University of Texas-M.D. Anderson Cancer Center, Houston, Texas, USA
    Maki Wakamiya & Richard R. Behringer

Authors

  1. Wanting Xu
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  2. Diane G. Edmondson
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  3. Yvonne A. Evrard
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  4. Maki Wakamiya
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  5. Richard R. Behringer
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  6. Sharon Y. Roth
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Corresponding author

Correspondence toSharon Y. Roth.

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Xu, W., Edmondson, D., Evrard, Y. et al. Loss of Gcn5l2 leads to increased apoptosis and mesodermal defects during mouse development.Nat Genet 26, 229–232 (2000). https://doi.org/10.1038/79973

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