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RRC ID 88557
著者 Nakata Y, Nagasawa S, Sera Y, Yamasaki N, Kanai A, Kobatake K, Ueda T, Koizumi M, Manabe I, Kaminuma O, Honda H.
タイトル PTIP epigenetically regulates DNA damage-induced cell cycle arrest by upregulating PRDM1.
ジャーナル Sci Rep
Abstract The genome is constantly exposed to DNA damage from endogenous and exogenous sources. Fine modulation of DNA repair, chromatin remodeling, and transcription factors is necessary for protecting genome integrity, but the precise mechanisms are still largely unclear. We found that after ionizing radiation (IR), global trimethylation of histone H3 at lysine 4 (H3K4me3) was decreased at an early (5 min) post-IR phase but increased at an intermediate (180 min) post-IR phase in both human and mouse hematopoietic cells. We demonstrated that PTIP, a component of the MLL histone methyltransferase complex, is required for H3K4me3 upregulation in the intermediate post-IR phase and promotes cell cycle arrest by epigenetically inducing a cell cycle inhibitor, PRDM1. In addition, we found that PTIP expression is specifically downregulated in acute myeloid leukemia patients. These findings collectively suggest that the PTIP-PRDM1 axis plays an essential role in proper DNA damage response and its deregulation contributes to leukemogenesis.
巻・号 14(1)
ページ 17987
公開日 2024-8-3
DOI 10.1038/s41598-024-68295-w
PII 10.1038/s41598-024-68295-w
PMID 39097652
PMC PMC11297997
MeSH Animals Carrier Proteins / genetics Carrier Proteins / metabolism Cell Cycle Checkpoints* DNA Damage* DNA-Binding Proteins* / genetics DNA-Binding Proteins* / metabolism Epigenesis, Genetic Histones / metabolism Humans Leukemia, Myeloid, Acute / genetics Leukemia, Myeloid, Acute / metabolism Leukemia, Myeloid, Acute / pathology Mice Nuclear Proteins / genetics Nuclear Proteins / metabolism Positive Regulatory Domain I-Binding Factor 1* / genetics Positive Regulatory Domain I-Binding Factor 1* / metabolism Radiation, Ionizing Up-Regulation
リソース情報
実験動物マウス RBRC01828