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Human Arf tumor suppressor specifically interacts with chromatin containing the promoter of rRNA genes

Abstract

The tumor suppressor Arf (Alternative Reading Frame) protein (p14ARF in human and p19ARF in mouse) is mainly located in the nucleolus consistent with its subcellular localization, the protein has been shown to specifically interact with 5.8S rRNA and with B23/Nucleophosmin and to regulate ribosome biogenesis. Here, we show that the p14ARF protein interacts with chromatin and is recovered by chromatin immunoprecipitation (ChIP) in a fraction that contains a DNA sequence of the rRNA gene promoter. In addition, topoisomerase I (Topo I) that has been shown to interact with p14ARF coprecipitates with p14ARF containing chromatin. These data, in view of the function for Topo I in rRNA transcription, are consistent with a role for the p14ARF-Topo I complex in rRNA transcription and/or maturation.

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Acknowledgements

This work was supported by a Grant from the ‘Ligue contre le Cancer, comité de la Vienne’. We are grateful to Dr Annick Harel-Bellan who welcomed O Ayrault in her laboratory and to Irina Naguibneva who provided precious help and advices for ChIP technique. L Andrique is currently supported by a grant from the ‘Ligue Nationale Contre le Cancer’. We also wish to thank the ‘Société française du Cancer’ for financial support of O Ayrault during his stay in Dr Harel-Bellan laboratory.

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Correspondence to Paule Seite.

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Ayrault, O., Andrique, L., Larsen, CJ. et al. Human Arf tumor suppressor specifically interacts with chromatin containing the promoter of rRNA genes. Oncogene 23, 8097–8104 (2004). https://doi.org/10.1038/sj.onc.1207968

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