| First Author | Tanikawa C | Year | 2012 |
| Journal | Nat Commun | Volume | 3 |
| Pages | 676 | PubMed ID | 22334079 |
| Mgi Jnum | J:260360 | Mgi Id | MGI:6149851 |
| Doi | 10.1038/ncomms1676 | Citation | Tanikawa C, et al. (2012) Regulation of histone modification and chromatin structure by the p53-PADI4 pathway. Nat Commun 3:676 |
| abstractText | 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. |
