Histone H3K9 methylation promotes formation of genome compartments in Caenorhabditis elegans via chromosome compaction and perinuclear anchoring
Histone H3K9 methylation promotes formation of genome compartments in Caenorhabditis elegans via chromosome compaction and perinuclear anchoring
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组蛋白 H3K9 甲基化通过染色体压缩和核周锚定促进秀丽隐杆线虫基因组区室的形成
DOI：
10.1073/pnas.2002068117
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发表时间：
2020-05-26
影响因子：
11.1
通讯作者：
Meyer, Barbara J.
中科院分区：
文献类型：
--
作者：
Bian, Qian;Anderson, Erika C.;Meyer, Barbara J.
基因组区域优先与具有相似转录活性的区域相关联，将基因组划分为核内的活性区室和非活性区室。在此，我们探讨机制控制基因组隔间组织秀丽隐杆线虫和调查的作用，车厢在调节基因表达。C远侧臂富含异染色质组蛋白修饰H3 K9 me 1/me 2/me 3的线虫染色体以顺式和反式相互作用，而与中心区域的相互作用频率较低，导致基因组区室化。臂通过与H3 K9 me结合的核膜蛋白CEC-4锚定到核外周。通过进行全基因组染色体构象捕获实验（Hi-C），我们表明通过甲基转移酶基因met-2和set-25中的突变消除H3 K9 me 1/me 2/me 3显著损害了非活性臂和活性中心区室的形成。CEC-4突变也损害区室化，但程度较低。我们发现H3 K9 me通过两种不同的机制促进区室化：通过CEC-4促进其顺式缔合的染色体臂的核周锚定，以及压缩单个染色体臂的锚定独立机制。在met-2 set-25和cec-4突变体中，没有发现基因表达的显著变化，无论是转换区室的基因还是保留在原始区室的基因，这表明区室强度并不决定基因表达水平。此外，H3 K9 me，而不是核周锚定，也有助于形成染色体组织的另一个突出特征，即由剂量补偿缩合素复合物建立的X上的兆碱基规模拓扑关联结构域。我们的研究结果表明，H3 K9 me在多个水平上调节基因组组织中起着至关重要的作用。
Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Herewe explore mechanisms controlling genome compartment organization in Caenorhabditis elegans and investigate roles for compartments in regulating gene expression. Distal arms of C. elegans chromosomes, which are enriched for heterochromatic histone modifications H3K9me1/ me2/me3, interact with each other both in cis and in trans, while interacting less frequently with central regions, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genes met-2 and set-25 significantly impaired formation of inactive Arm and active Center compartments. cec-4 mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: Perinuclear anchoring of chromosome arms via CEC-4 to promote their cis association, and an anchoring-independent mechanism that compacts individual chromosome arms. In both met-2 set-25 and cec-4 mutants, no dramatic changes in gene expressionwere found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene-expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X established by the dosage compensation condensin complex. Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels.