Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403
Faculty of Medical Sciences, University of Fukui, 910-1193, Japan.
Genetics. 2019 Feb;211(2):563-578. doi: 10.1534/genetics.118.301711. Epub 2018 Dec 15.
In the filamentous fungus , constitutive heterochromatin is marked by tri-methylation of histone H3 lysine 9 (H3K9me3) and DNA methylation. We identified mutations in the defective in methylation-1 () gene that cause defects in cytosine methylation and implicate a putative AAA-ATPase chromatin remodeler. Although it was well-established that chromatin remodelers can affect transcription by influencing DNA accessibility with nucleosomes, little was known about the role of remodelers on chromatin that is normally not transcribed, including regions of constitutive heterochromatin. We found that mutants display both reduced DNA methylation in heterochromatic regions as well as increased DNA methylation and H3K9me3 in some intergenic regions associated with highly expressed genes. Deletion of leads to atypically spaced nucleosomes throughout the genome and numerous changes in gene expression. DIM-1 localizes to both heterochromatin and intergenic regions that become hyper-methylated in strains. Our findings indicate that DIM-1 normally positions nucleosomes in both heterochromatin and euchromatin and that the standard arrangement and density of nucleosomes is required for the proper function of heterochromatin machinery.
在丝状真菌中，组成型异染色质的特征是组蛋白 H3 赖氨酸 9（H3K9me3）的三甲基化和 DNA 甲基化。我们鉴定了 基因（defective in methylation-1， ）中的突变，这些突变导致胞嘧啶甲基化缺陷，并暗示了一个假定的 AAA-ATPase 染色质重塑因子。尽管已经证实染色质重塑因子可以通过影响核小体的 DNA 可及性来影响转录，但对于通常不转录的染色质（包括组成型异染色质区域）的重塑因子的作用知之甚少。我们发现， 突变体在异染色质区域的 DNA 甲基化减少，以及与高度表达基因相关的一些基因间区域的 DNA 甲基化和 H3K9me3 增加。 缺失导致整个基因组中核小体的间隔异常，并导致许多基因表达的变化。DIM-1 定位于异染色质和基因间区域，在 菌株中这些区域变得过度甲基化。我们的发现表明，DIM-1 通常将核小体定位在异染色质和常染色质中，并且核小体的标准排列和密度是异染色质机制正常功能所必需的。
