HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 26, 18218-18226, June 27, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/26/18218    most recent M802332200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Miyamoto, N. Articles by Kohno, K. PubMed PubMed Citation Articles by Miyamoto, N. Articles by Kohno, K. Social Bookmarking                      What's this?

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, and Kimitoshi Kohno¹

From the Departments of Molecular Biology and Ophthalmology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, ^¶National Institute of Advanced Industrial Science and Technology, Osaka, 563-8577, and ^||Department of Photobiology, Hokkaido University Graduate School of Medicine, Sapporo, 060-8633, Japan

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. Tip60 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.

Received for publication, March 25, 2008 , and in revised form, May 5, 2008.

^* This work was supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Kakenhi) Grants 13218132 and 18590307, by the Kobayashi Institute for Innovative Cancer Chemotherapy, and by a grant-in-aid for Cancer Research from the Fukuoka Cancer Society, Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 81-93-691-7423; Fax: 81-93-692-2766; E-mail: k-kohno{at}med.uoeh-u.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?