Tip60 is regulated by circadian transcription factor clock and is involved in cisplatin resistance

Naoya Miyamoto, Hiroto Izumi, Takako Noguchi, Yoshihiro Nakajima, Yoshihiro Ohmiya, Masaki Shiota, Akihiko Kidani, Akihiko Tawara, Kimitoshi Kohno

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)


Histone modification is important for maintaining chromatin structure and function. Recently, histone acetylation has been shown to have a critical regulatory role in both transcription and DNA repair. We report here that expression of histone acetyltransferase (HAT) genes is associated with cisplatin resistance. We found that Tip60 is overexpressed in cisplatin-resistant cells. The expression of two other HAT genes, HAT1 and MYST1, did not differ between drug-sensitive and -resistant cells. Knockdown of Tip60 expression rendered cells sensitive to cisplatin but not to oxaliplatin, vincristine, and etoposide. Tip 60 expression is significantly correlated with cisplatin sensitivity in human lung cancer cell lines. Interestingly, the promoter region of the Tip60 gene contains several E boxes, and its expression was regulated by the E-box binding circadian transcription factor Clock but not by other E-box binding transcription factors such as c-Myc, Twist, and USF1. Hyperacetylation of H3K14 and H4K16 was found in cisplatin-resistant cells. The microarray study reveals that several genes for DNA repair are down-regulated by the knockdown of Tip60 expression. Our data show that HAT gene expression is required for cisplatin resistance and suggest that Clock and Tip60 regulate not only transcription, but also DNA repair, through periodic histone acetylation.

Original languageEnglish
Pages (from-to)18218-18226
Number of pages9
JournalJournal of Biological Chemistry
Issue number26
Publication statusPublished - Jun 27 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Tip60 is regulated by circadian transcription factor clock and is involved in cisplatin resistance'. Together they form a unique fingerprint.

Cite this