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

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holling, T. M. Articles by Van den Elsen, P. J. Search for Related Content PubMed PubMed Citation Articles by Holling, T. M. Articles by Van den Elsen, P. J.

A Role for EZH2 in Silencing of IFN- Inducible MHC2TA Transcription in Uveal Melanoma¹

Tjadine M. Holling^*, Marloes W. T. Bergevoet^*, Louis Wilson^*, Marja C. J. A. Van Eggermond^*, Erik Schooten^*, Renske D. M. Steenbergen, Peter J. F. Snijders, Martine J. Jager and Peter J. Van den Elsen^2,*,

^* Division of Molecular Biology, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands; and Department of Pathology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands

We investigated the contribution of epigenetic mechanisms in MHC2TA transcriptional silencing in uveal melanoma. Although no correlation was observed between impaired CIITA transcript levels after IFN- induction and DNA methylation of MHC2TA promoter IV (CIITA-PIV), an association was found with high levels of trimethylated histone H3-lysine 27 (3Me-K27-H3) in CIITA-PIV chromatin. The 3Me-K27-H3 modification correlated with a strong reduction in RNA polymerase II-recruitment to CIITA-PIV. Interestingly, we observed that none of these epigenetic modifications affected recruitment of activating transcription factors to this promoter. Subsequently, we demonstrated the presence of the histone methyltransferase EZH2 in CIITA-PIV chromatin, which is known to be a component of the Polycomb repressive complex 2 and able to triple methylate histone H3-lysine 27. RNA interference-mediated down-regulation of EZH2 expression resulted in an increase in CIITA transcript levels after IFN- induction. Our data therefore reveal that EZH2 contributes to silencing of IFN--inducible transcription of MHC2TA in uveal melanoma cells.

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 This research was supported by a grant from the Dutch Cancer Society (RUL 03–2798). R.D.M.S. is a fellow of the Royal Netherlands Academy for Arts and Sciences.

² Address correspondence and reprint requests to Dr. Peter J. van den Elsen, Department of Immunohematology and Blood Transfusion, Division of Molecular Biology, Building 1, E3-Q, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands. E-mail address: pjvdelsen{at}lumc.nl

³ Abbreviations used in this paper: PRC, Polycomb repressive complex; Dnmt, DNA methyltransferase; ChIP, chromatin immunoprecipitation; HDAC, histone deacetylase.

This article has been cited by other articles:

				H. F. Kuipers, P. J. Biesta, L. J. Montagne, E. S. van Haastert, P. van der Valk, and P. J. van den Elsen CC chemokine receptor 5 gene promoter activation by the cyclic AMP response element binding transcription factor Blood, September 1, 2008; 112(5): 1610 - 1619. [Abstract] [Full Text] [PDF]