Polycomb "polypacks" the chromatin.
Polycomb "polypacks" the chromatin.
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Polycomb 对染色质进行“聚合包装”。
DOI：
10.1073/pnas.1618224114
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发表时间：
2016
影响因子：
11.1
通讯作者：
Zhu Bing
中科院分区：
文献类型：
--
作者：
Xiong Jun;Zhang Zhuqiang;Zhu Bing
几十年来，研究人员付出了巨大的努力来表征细胞核中的染色体组织。随着染色体构象捕获 (1) 和相关技术的发展，研究人员已开始在分子水平上深入了解染色体间和染色体内接触的形成方式。对后生动物接触频率的定量测量表明拓扑关联域 (TAD) 的存在作为染色体组织的构建块 (1-3)。这些结构域通常由不同的组蛋白修饰模式划分。例如，富含 H3K27me3 和耗尽 H3K36me3 的区室是人类基因组中兼性异染色质的特征。尽管染色体组织的特征已经在多种生物体中得到表征，但控制染色体组织形成的原理和机制仍然是个谜。在 PNAS 中，Klocko 等人 (4) 报告称，多梳抑制复合体 2 (PRC2) 和 H3K27me3 在塑造粗糙脉孢菌的基因组组织中发挥作用。在哺乳动物和果蝇细胞中，染色体被分离成大的 TAD，相邻 TAD 之间的边界以富集的绝缘体蛋白 CTCF 占据为特征 (2, 3)。植物、酵母和粗糙脉孢菌的基因组中缺乏大的局部相互作用域，这可能是编码 CTCF 蛋白的基因丢失的结果 (5, 6)。植物和粗糙脉孢菌基因组中最明显的染色体接触是在异染色质区域之间形成的。然而，H3K9me3 和组成型异染色质机制对于这种接触似乎是可有可无的 (5, 6)。裂殖酵母不具有 H3K27 甲基化，其唯一的 H3K9 甲基转移酶是正确基因组组织所必需的 (7)。这一结果提出了 H3K27 甲基化和兼性异染色质是否有助于基因组结构形成的问题。
For decades, researchers have made a tremendous effort to characterize the chromosome organization in the nucleus. With the development of chromosome conformation capture (1) and related techniques, researchers have begun to gain insight at the molecular level into how inter-and intrachromosome contacts are formed. Quantitative measurement of the contact frequencies in metazoans suggested the existence of topologically associating domains (TADs) as the building blocks of chromosome organization (1–3). These domains are often demarcated by distinct patterns of histone modifications. For example, compartments that are enriched with H3K27me3 and have depleted H3K36me3 are signatures of facultative heterochromatin in the human genome. Although the features of chromosome organization have been characterized in several organisms, the principles and mechanisms governing the formation of chromosome organization have remained a mystery. In PNAS, Klocko et al.(4) report that the Polycomb Repressive Complex 2 (PRC2) and H3K27me3 have a role in shaping genome organization in Neurospora crassa.In mammalian and Drosophila cells, chromosomes are segregated into large TADs, and boundaries between adjacent TADs are characterized by enriched insulator protein CTCF occupancy (2, 3). Plants, yeast, and N. crassa lack large local interactive domains in their genomes, which is likely a result of the loss of genes encoding the CTCF protein (5, 6). The most obvious chromosomal contacts in plants and N. crassa genomes are formed between heterochromatin regions. However, H3K9me3 and the constitutive heterochromatin machinery seemed to be dispensable for this contact (5, 6). Fission yeast does not have H3K27 methylation, and its sole H3K9 methyltransferase is needed for proper genome organization (7). This result raises the question of whether H3K27 methylation and facultative heterochromatin contribute to genome structure formation.