CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis

Masaaki Nishiyama, Kiyotaka Oshikawa, Yu Ichi Tsukada, Tadashi Nakagawa, Shun Ichiro Iemura, Tohru Natsume, Yuhong Fan, Akira Kikuchi, Arthur I. Skoultchi, Keiichi I. Nakayama

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Abstract

The chromodomain helicase DNA-binding (CHD) family of enzymes is thought to regulate gene expression, but their role in the regulation of specific genes has been unclear. Here we show that CHD8 is expressed at a high level during early embryogenesis and prevents apoptosis mediated by the tumour suppressor protein p53. CHD8 was found to bind to p53 and to suppress its transactivation activity. CHD8 promoted the association of p53 and histone H1, forming a trimeric complex on chromatin that was required for inhibition of p53-dependent transactivation and apoptosis. Depletion of CHD8 or histone H1 resulted in p53 activation and apoptosis. Furthermore, Chd8-/- mice died early during embryogenesis, manifesting widespread apoptosis, whereas deletion of p53 ameliorated this developmental arrest. These observations reveal a mode of p53 regulation mediated by CHD8, which may set a threshold for induction of apoptosis during early embryogenesis by counteracting p53 function through recruitment of histone H1.

Original languageEnglish (US)
Pages (from-to)172-182
Number of pages11
JournalNature Cell Biology
Volume11
Issue number2
DOIs
StatePublished - 2009

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Histones
Embryonic Development
Apoptosis
Transcriptional Activation
DNA Helicases
Tumor Suppressor Protein p53
Chromatin
Gene Expression
Enzymes
Genes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Nishiyama, M., Oshikawa, K., Tsukada, Y. I., Nakagawa, T., Iemura, S. I., Natsume, T., ... Nakayama, K. I. (2009). CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. Nature Cell Biology, 11(2), 172-182. https://doi.org/10.1038/ncb1831

CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. / Nishiyama, Masaaki; Oshikawa, Kiyotaka; Tsukada, Yu Ichi; Nakagawa, Tadashi; Iemura, Shun Ichiro; Natsume, Tohru; Fan, Yuhong; Kikuchi, Akira; Skoultchi, Arthur I.; Nakayama, Keiichi I.

In: Nature Cell Biology, Vol. 11, No. 2, 2009, p. 172-182.

Research output: Contribution to journalArticle

Nishiyama, M, Oshikawa, K, Tsukada, YI, Nakagawa, T, Iemura, SI, Natsume, T, Fan, Y, Kikuchi, A, Skoultchi, AI & Nakayama, KI 2009, 'CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis', Nature Cell Biology, vol. 11, no. 2, pp. 172-182. https://doi.org/10.1038/ncb1831
Nishiyama M, Oshikawa K, Tsukada YI, Nakagawa T, Iemura SI, Natsume T et al. CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. Nature Cell Biology. 2009;11(2):172-182. https://doi.org/10.1038/ncb1831
Nishiyama, Masaaki ; Oshikawa, Kiyotaka ; Tsukada, Yu Ichi ; Nakagawa, Tadashi ; Iemura, Shun Ichiro ; Natsume, Tohru ; Fan, Yuhong ; Kikuchi, Akira ; Skoultchi, Arthur I. ; Nakayama, Keiichi I. / CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. In: Nature Cell Biology. 2009 ; Vol. 11, No. 2. pp. 172-182.
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