Department of Molecular Biology, University of California, San Diego, La Jolla, CA 92093, USA.
Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75246, USA.
Cell Rep. 2020 Apr 7;31(1):107470. doi: 10.1016/j.celrep.2020.03.034.
The transition from the follicular B to the plasma cell stage is associated with large-scale changes in cell morphology. Here, we examine whether plasma cell development is also associated with changes in nuclear architecture. We find that the onset of plasma cell development is concomitant with a decline in remote genomic interactions; a gain in euchromatic character at loci encoding for factors that specify plasma cell fate, including Prdm1 and Atf4; and establishment of de novo inter-chromosomal hubs. We find that, in developing plasma cells and concurrent with transcriptional silencing, the Ebf1 locus repositions from an euchromatic to peri-centromeric heterochromatic environment. Finally, we find that inter-chromosomal hubs are enriched for the deposition of either H3K27Ac or H3K27me3. These data indicate that plasma cell fate is orchestrated by elaborate changes in genome topology and that epigenetic marks, linked with super-enhancers or transcriptionally repressed regions, are enriched at inter-chromosomal hubs.
从滤泡 B 细胞向浆细胞阶段的过渡与细胞形态的大规模变化有关。在这里，我们研究浆细胞发育是否也与核架构的变化有关。我们发现，浆细胞发育的开始伴随着远程基因组相互作用的减少；编码指定浆细胞命运的因子（包括 Prdm1 和 Atf4）的基因座上的常染色质特征增加；以及从头建立染色体间枢纽。我们发现，在发育中的浆细胞中，与转录沉默同时发生，Ebf1 基因座从常染色质重新定位到着丝粒周围异染色质环境。最后，我们发现染色体间枢纽富含 H3K27Ac 或 H3K27me3 的沉积。这些数据表明，浆细胞命运是由基因组拓扑结构的精细变化来协调的，与超级增强子或转录抑制区域相关的表观遗传标记在染色体间枢纽处富集。
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