Nucleosome Positioning by an Evolutionarily Conserved Chromatin Remodeler Prevents Aberrant DNA Methylation in Neurospora
Nucleosome Positioning by an Evolutionarily Conserved Chromatin Remodeler Prevents Aberrant DNA Methylation in Neurospora
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DOI：
10.1534/genetics.118.301711
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发表时间：
2019-02-01
期刊：
影响因子：
3.3
通讯作者：
Selker, Eric U.
中科院分区：
文献类型：
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作者：
Klocko, Andrew D.;Uesaka, Miki;Selker, Eric U.
在丝状真菌粗糙脉孢菌中，组成型异染色质由组蛋白H3赖氨酸9（H3 K9 me 3）的三甲基化和DNA甲基化标记。我们鉴定了脉孢菌甲基化缺陷1（dim-1）基因的突变，该突变导致胞嘧啶甲基化缺陷，并暗示了假定的AAA-ATP酶染色质重塑。虽然它是公认的，染色质重塑可以通过影响DNA与核小体的可及性影响转录，很少有人知道重塑染色质的作用，通常是不转录，包括组成型异染色质的区域。我们发现dim-1突变体在异染色质区域显示DNA甲基化降低，在与高表达基因相关的一些基因间区域显示DNA甲基化和H3 K9 me 3增加。dim-1的缺失导致整个基因组中的核小体间隔排列，并导致基因表达的许多变化。DIM-1定位于异染色质和基因间区域，这些区域在dim-1菌株中变得高度甲基化。我们的研究结果表明，DIM-1通常在异染色质和常染色质中定位核小体，并且核小体的标准排列和密度是异染色质机器正常功能所必需的。
In the filamentous fungus Neurospora crassa, constitutive heterochromatin is marked by tri-methylation of histone H3 lysine 9 (H3K9me3) and DNA methylation. We identified mutations in the Neurospora defective in methylation-1 (dim-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 dim-1 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 dim-1 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 dim-1 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.