High impact information on DDM1

• Using a forward genetic screen, we identified a gene (DDM1, decrease in DNA methylation) from the flowering plant Arabidopsis thaliana required to maintain normal cytosine methylation patterns [1].
• Loss of DDM1 function causes a 70% reduction of genomic cytosine methylation, with most of the immediate hypomethylation occurring in repeated sequences [1].
• Additional ddm1 alleles (som4, 5, 6, 7, 8) were isolated in a selection for mutations that relieved transgene silencing (E.J.R., unpublished data) [1].
• Thus the DDM1 gene not only epigenetically ensures proper gene expression, but also stabilizes transposon behaviour, possibly through chromatin remodelling or DNA methylation [2].
• Robertson's Mutator transposons in A. thaliana are regulated by the chromatin-remodeling gene Decrease in DNA Methylation (DDM1) [3].

Biological context of DDM1

• The DNA methylation locus DDM1 is required for maintenance of gene silencing in Arabidopsis [4].
• In the first generation, homozygous ddm1 MePAI2 plants displayed a weakly fluorescent phenotype, in contrast to the strongly fluorescent phenotype of the DDM1 MePAI2 parent [4].
• The enzymatic activity of DDM1 is not affected by DNA methylation [5].
• Thus, unlike the SNF2-like proteins DDM1/Lsh1 and ATRX, which regulate methylation of repetitive sequences, DRD1 is not a global regulator of cytosine methylation [6].
• DDM1 binds to the nucleosome and promotes chromatin remodeling in an ATP-dependent manner [5].

Associations of DDM1 with chemical compounds

• In addition, DDM1 is required for deacetylation of histone H4 lysine 16 [7].
• We have recently isolated two Arabidopsis thaliana DNA hypomethylation mutations, identifying the DDM1 locus, that cause a 70% reduction in genomic 5-methylcytosine levels [1] [8].
• The female-gametophytic effects on embryo and endosperm development in the Arabidopsis mea, fis, and fie mutants appear to be due to gametic imprinting that can be suppressed by METHYL TRANSFERASE1 antisense (MET1 a/s) transgene expression or by mutation of the DECREASE IN DNA METHYLATION1 (DDM1) gene [9].
• AFLP can detect genome-wide changes in cytosine methylation produced by DNA demethylation agents, such as 5-azacytidine, or specific mutations at the DDM1 locus [10].
• However, rather than encoding a DNA methyltransferase, DDM1 has similarity to the SWI/SNF family of adenosine triphosphate-dependent chromatin remodeling genes, suggesting an indirect role in DNA methylation [11].

Other interactions of DDM1

• In addition, genes known for their role in development, such as PICKLE/GYMNOS and PIE1, or in silencing, such as DDM1, turned out to also be involved in DNA damage response [12].
• Maintenance of genomic imprinting at the Arabidopsis medea locus requires zygotic DDM1 activity [13].
• This histone methylation is dependent on the KRYPTONITE and DDM1 genes (SU[VAR]3-9 and SWI2/SNF2 homologs, respectively) [14].
• DDM1 and MET1 control heterochromatin assembly at chromocenters by their influence on DNA maintenance (CpG) methylation and subsequent methylation of histone H3 lysine 9 [7].
• The synergistic release of TGS revealed by gene expression patterns from silent loci, drastic developmental abnormalities, and characteristic changes in nuclear architecture in these double mutants implies that DDM1 and MOM are likely to operate at independent levels in TGS control [15].

References