4.6 Article

Histone XH2AX Is Required for Xenopus Anterior Neural Development CRITICAL ROLE OF THREONINE 16 PHOSPHORYLATION

Journal

JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 38, Pages 29525-29534

Publisher

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.127233

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Funding

  1. National Institutes of Health [CA077646, CA111536, CA120388, R37 CA081064, ES016548]
  2. Hormel Foundation

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A role for histone H2AX, one of the variants of the nucleosome core histone H2A, has been demonstrated in DNA repair, tumor suppression, apoptosis, and cell cycle checkpoint function. However, the physiological function and post-translational modification of histone H2AX during vertebrate development have not been elucidated. Here, we provide evidence showing that Xenopus histone H2AX (XH2AX) has a role in the anterior neural plate for eye field formation during Xenopus embryogenesis. A loss-of-function study clearly demonstrated a critical role of XH2AX in anterior neural specification. Through a differentiation assay with Xenopus animal cap embryonic stem cells, we confirmed that XH2AX is required for the activin-induced anterior neural specification of the ectoderm. Furthermore, we found that Chk1 is an essential kinase to phosphorylate histone XH2AX at Thr(16), which is involved in the biological function of this histone. Taken together, our findings reveal that XH2AX has a specific role in anterior neural formation of Xenopus, which is mediated through phosphorylation of XH2AX at Thr(16) by Chk1.

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