Histone H3 K4 demethylation during activation and attenuation of GAL1 transcription in Saccharomyces cerevisiae.
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.
Ingvarsdottir
Kristin
K
Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Edwards
Chris
C
Lee
Min Gyu
MG
Lee
Jung Shin
JS
Schultz
David C
DC
Shilatifard
Ali
A
Shiekhattar
Ramin
R
Berger
Shelley L
SL
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D005686:Galactokinase / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D043324:beta-Fructofuranosidase / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D010089:Oxidoreductases, N-Demethylating; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; C524219:GAL1 protein, S cerevisiae; D005686:Galactokinase; C468437:SUC2 protein, S cerevisiae; D043324:beta-Fructofuranosidase; D008239:Lysine