Department of Biology and Institute of Molecular Biology, University of Oregon, Eugene, 97403, USA.
Genes Dev. 2010 Mar 1;24(5):443-54. doi: 10.1101/gad.1893210. Epub 2010 Feb 5.
Transposable elements are common in genomes and must be controlled. Many organisms use DNA methylation to silence such selfish DNA, but the mechanisms that restrict the methylation to appropriate regions are largely unknown. We identified a JmjC domain protein in Neurospora, DNA METHYLATION MODULATOR-1 (DMM-1), that prevents aberrant spreading of DNA and histone H3K9 methylation from inactivated transposons into nearby genes. Mutation of a conserved residue within the JmjC Fe(II)-binding site abolished dmm-1 function, as did mutations in conserved cysteine-rich domains. Mutants defective only in dmm-1 mutants grow poorly, but growth is restored by reduction or elimination of DNA methylation using the drug 5-azacytosine or by mutation of the DNA methyltransferase gene dim-2. DMM-1 relies on an associated protein, DMM-2, which bears a DNA-binding motif, for localization and proper function. HP1 is required to recruit the DMM complex to the edges of methylated regions.
转座元件在基因组中很常见，必须加以控制。许多生物利用 DNA 甲基化来使这些自私的 DNA 沉默，但限制甲基化到适当区域的机制在很大程度上是未知的。我们在Neurospora 中鉴定了一种 JmjC 结构域蛋白，即 DNA 甲基化调节剂-1（DMM-1），它可以防止失活转座子的 DNA 和组蛋白 H3K9 甲基化异常扩散到附近的基因中。在 JmjC Fe(II)结合位点内的保守残基发生突变会使 dmm-1 功能丧失，而保守的富含半胱氨酸的结构域发生突变也会使 dmm-1 功能丧失。仅在 dmm-1 突变体中发生突变的突变体生长不良，但通过使用药物 5-氮胞苷减少或消除 DNA 甲基化，或通过突变 DNA 甲基转移酶基因 dim-2，可以恢复生长。DMM-1 依赖于与其相关的蛋白 DMM-2，后者具有 DNA 结合基序，用于定位和正常功能。HP1 被招募到甲基化区域的边缘。
