A histone H3 methyltransferase controls DNA methylation in Neurospora crassa.
DNA methylation is involved in epigenetic processes such as X-chromosome inactivation, imprinting and silencing of transposons. We have demonstrated previously that dim-2 encodes a DNA methyltransferase that is responsible for all known cytosine methylation in Neurospora crassa. Here we report that another Neurospora gene, dim-5, is required for DNA methylation, as well as for normal growth and full fertility. We mapped dim-5 and identified it by transformation with a candidate gene. The mutant has a nonsense mutation in a SET domain of a gene related to histone methyltransferases that are involved in heterochromatin formation in other organisms. Transformation of a wild-type strain with a segment of dim-5 reactivated a silenced hph gene, apparently by 'quelling' of dim-5. We demonstrate that recombinant DIM-5 protein specifically methylates histone H3 and that replacement of lysine 9 in histone H3 with either a leucine or an arginine phenocopies the dim-5 mutation. We conclude that DNA methylation depends on histone methylation.
Tamaru
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Institute of Molecular Biology, University of Oregon, Eugene 97403-1229, USA.
Selker
E U
EU
D000595:Amino Acid Sequence; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D002874:Chromosome Mapping; D015825:Chromosomes, Fungal; D018389:Codon, Nonsense; D019175:DNA Methylation; D004271:DNA, Fungal / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009492:Neurospora crassa / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames; D011496:Protein Methyltransferases; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D016415:Sequence Alignment; D015398:Signal Transduction; D014157:Transcription Factors; D019076:Transgenes
D002868:Chromosomal Proteins, Non-Histone; D018389:Codon, Nonsense; D004271:DNA, Fungal; D006570:Heterochromatin; D006657:Histones; D011506:Proteins; D014157:Transcription Factors; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine