Regulation of histone modification and chromatin structure by the p53–PADI4 pathway

Chizu Tanikawa, Martha Espinosa, Akari Suzuki, Ken Masuda, Kazuhiko Yamamoto, Eiju Tsuchiya, Koji Ueda, Yataro Daigo, Yusuke Nakamura and Koichi Matsuda ()
Additional contact information
Chizu Tanikawa: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo
Martha Espinosa: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo
Akari Suzuki: Laboratory for Rheumatic Diseases, Center for Genomic Medicine, RIKEN
Ken Masuda: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo
Kazuhiko Yamamoto: Laboratory for Rheumatic Diseases, Center for Genomic Medicine, RIKEN
Eiju Tsuchiya: Saitama Cancer Center
Koji Ueda: Laboratory for Biomarker Development, Center for Genomic Medicine, RIKEN
Yataro Daigo: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo
Yusuke Nakamura: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo
Koichi Matsuda: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo

Nature Communications, 2012, vol. 3, issue 1, 1-11

Abstract: Abstract Histone proteins are modified in response to various external signals; however, their mechanisms are still not fully understood. Citrullination is a post-transcriptional modification that converts arginine in proteins into citrulline. Here we show in vivo and in vitro citrullination of the arginine 3 residue of histone H4 (cit-H4R3) in response to DNA damage through the p53–PADI4 pathway. We also show DNA damage-induced citrullination of Lamin C. Cit-H4R3 and citrullinated Lamin C localize around fragmented nuclei in apoptotic cells. Ectopic expression of PADI4 leads to chromatin decondensation and promotes DNA cleavage, whereas Padi4−/− mice exhibit resistance to radiation-induced apoptosis in the thymus. Furthermore, the level of cit-H4R3 is negatively correlated with p53 protein expression and with tumour size in non-small cell lung cancer tissues. Our findings reveal that cit-H4R3 may be an 'apoptotic histone code' to detect damaged cells and induce nuclear fragmentation, which has a crucial role in carcinogenesis.

Date: 2012
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms1676 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1676

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1676

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().