将基因组组织成常染色质和异染色质似乎在进化上是保守的，并且在谱系分化过程中相对稳定。为了阐明基因组折叠的基本原理，我们在这里关注基因组本身并报告 L1（LINE1 或 LINE-1）和 B1/Alu 反转录转座子（重复序列中最丰富的亚类）在染色质区室化中的基本作用. 我们发现 L1 和 B1/Alu 的同型聚类将基因组划分为完全排他的域，并表征和预测 Hi-C 区室。细胞核和核仁周围富含 L1 的序列和细胞核内部富含 B1/Alu 的序列的空间分离在小鼠和人类细胞中是保守的，并且在细胞周期中动态发生。此外，L1 和 B1 核分离的从头建立与早期胚胎发生过程中高阶染色质结构的形成同时发生，并且似乎受到 L1 和 B1 转录本的严格调控。重要的是，胚胎干细胞中 L1 转录物的耗尽会大大削弱同型重复接触和区室强度，并破坏全基因组和单个位点富含 L1 或 B1 的染色体序列的核分离。从机制上讲，L1 重复 DNA 和 RNA 与异染色质蛋白 HP1α 的核共定位和液滴形成表明 L1 促进异染色质区室化的相分离机制。总之，我们提出了一个基因编码模型，其中 L1 和 B1/Alu 重复蓝图染色质宏观结构。

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Organization of the genome into euchromatin and heterochromatin appears to be evolutionarily conserved and relatively stable during lineage differentiation. In an effort to unravel the basic principle underlying genome folding, here we focus on the genome itself and report a fundamental role for L1 (LINE1 or LINE-1) and B1/Alu retrotransposons, the most abundant subclasses of repetitive sequences, in chromatin compartmentalization. We find that homotypic clustering of L1 and B1/Alu demarcates the genome into grossly exclusive domains, and characterizes and predicts Hi-C compartments. Spatial segregation of L1-rich sequences in the nuclear and nucleolar peripheries and B1/Alu-rich sequences in the nuclear interior is conserved in mouse and human cells and occurs dynamically during the cell cycle. In addition, de novo establishment of L1 and B1 nuclear segregation is coincident with the formation of higher-order chromatin structures during early embryogenesis and appears to be critically regulated by L1 and B1 transcripts. Importantly, depletion of L1 transcripts in embryonic stem cells drastically weakens homotypic repeat contacts and compartmental strength, and disrupts the nuclear segregation of L1- or B1-rich chromosomal sequences at genome-wide and individual sites. Mechanistically, nuclear co-localization and liquid droplet formation of L1 repeat DNA and RNA with heterochromatin protein HP1α suggest a phase-separation mechanism by which L1 promotes heterochromatin compartmentalization. Taken together, we propose a genetically encoded model in which L1 and B1/Alu repeats blueprint chromatin macrostructure. Our model explains the robustness of genome folding into a common conserved core, on which dynamic gene regulation is overlaid across cells.