Molecular Biology

Spreading Barrier

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Science  05 Mar 2010:
Vol. 327, Issue 5970, pp. 1181
DOI: 10.1126/science.327.5970.1181-b

DNA methylation generally functions to silence gene expression, and is most often targeted to parasitic and repeated sequences in the genome. Like other epigenetic marks, DNA methylation may be self-propagating, which can result in its inappropriate spreading into and silencing of nearby active genes. Clearly, barriers are needed to corral such silencing marks, and in yeast these consist of specific DNA sequences. In the filamentous fungus Neurospora, DNA methylation is found at AT-rich repeat sequences, including transposon relics and repetitive DNA, and Honda et al. show that spreading of DNA methylation into GC-rich regions that contain active genes is strictly limited by the protein DNA methylation modulator 1 (DMM1) and its binding partner DMM2. DDM1 and DMM2 are concentrated at the edges of methylated and silenced regions, and this localization depends on heterochromatin protein 1 (HP1) and histone H3 trimethylated on lysine 9 (H3K9me3), both of which are also implicated in silencing. DMM1 contains a Jumonji-C domain, which is known to direct histone demethylation in other Jumonji-C–containing proteins, and critical catalytic residues are required for the barrier activity of DMM1, suggesting that it might limit spreading by removing ectopic H3K9me3 marks, which recruit HP1, at the edges of methylated silencing domains.

Genes Dev. 24, 10.1101/gad.1893210 (2010).

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