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Molecular and Cellular Biology, November 2007, p. 7856-7864, Vol. 27, No. 22
0270-7306/07/$08.00+0     doi:10.1128/MCB.00801-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Histone H3 K4 Demethylation during Activation and Attenuation of GAL1 Transcription in Saccharomyces cerevisiae ^,

Kristin Ingvarsdottir,^1,2 Chris Edwards,^1,2 Min Gyu Lee,¹ Jung Shin Lee,³ David C. Schultz,¹ Ali Shilatifard,^3, Ramin Shiekhattar,¹ and Shelley L. Berger^1*

Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania,¹ Cell and Molecular Biology Program, University of Pennsylvania Medical School, Philadelphia, Pennsylvania,² Department of Biochemistry and Molecular Biology, Saint Louis University Health Sciences Center, St. Louis, Missouri³

Received 7 May 2007/ Returned for modification 15 June 2007/ Accepted 6 September 2007

In mammalian cells, histone lysine demethylation is carried out by two classes of enzymes, the LSD1/BHC110 class and the jumonji class. The enzymes of the jumonji class in the yeast Saccharomyces cerevisiae have recently also been shown to have lysine demethylation activity. Here we report that the protein encoded by YJR119c (termed KDM5), coding for one of five predicted jumonji domain proteins in yeast, specifically demethylates trimethylated histone H3 lysine 4 (H3K4me3), H3K4me2, and H3K4me1 in vitro. We found that loss of KDM5 increased mono-, di-, and trimethylation of lysine 4 during activation of the GAL1 gene. Interestingly, cells deleted of KDM5 also displayed a delayed reduction of K4me3 upon reestablishment of GAL1 repression. These results indicate that K4 demethylation has two roles at GAL1, first to establish appropriate levels of K4 methylation during gene activation and second to remove K4 trimethylation during the attenuation phase of transcription. Thus, analysis of lysine demethylation in yeast provides new insight into the physiological roles of jumonji demethylase enzymes.

Published ahead of print on 17 September 2007.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: Stowers Institute for Medical Research, Kansas City, MO.