Department of Epigenetic Mechanisms of Gene Expression Regulation, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology Russian Academy of Sciences, 119334 Moscow, Russia.
Int J Mol Sci. 2023 Jun 7;24(12):9842. doi: 10.3390/ijms24129842.
The expression of clusters of rDNA genes influences pluripotency; however, the underlying mechanisms are not yet known. These clusters shape inter-chromosomal contacts with numerous genes controlling differentiation in human and cells. This suggests a possible role of these contacts in the formation of 3D chromosomal structures and the regulation of gene expression in development. However, it has not yet been demonstrated whether inter-chromosomal rDNA contacts are changed during differentiation. In this study, we used human leukemia K562 cells and induced their erythroid differentiation in order to study both the changes in rDNA contacts and the expression of genes. We observed that approximately 200 sets of rDNA-contacting genes are co-expressed in different combinations in both untreated and differentiated K562 cells. rDNA contacts are changed during differentiation and coupled with the upregulation of genes whose products are mainly located in the nucleus and are highly associated with DNA- and RNA-binding, along with the downregulation of genes whose products mainly reside in the cytoplasm or intra- or extracellular vesicles. The most downregulated gene is , which is known as an inhibitor of differentiation, and thus should be switched off to allow for differentiation. Our data suggest that the differentiation of K562 cells leads to alterations in the inter-chromosomal contacts of rDNA clusters and 3D structures in particular chromosomal regions as well as to changes in the expression of genes located in the corresponding chromosomal domains. We conclude that approximately half of the rDNA-contacting genes are co-expressed in human cells and that rDNA clusters are involved in the global regulation of gene expression.
rDNA 基因簇的表达影响多能性；然而，其潜在机制尚不清楚。这些基因簇与许多控制人类和 细胞分化的基因形成染色体间接触。这表明这些接触可能在 3D 染色体结构的形成和发育过程中基因表达的调控中发挥作用。然而，尚未证明在分化过程中染色体间 rDNA 接触是否发生改变。在这项研究中，我们使用人白血病 K562 细胞并诱导其红细胞分化，以研究 rDNA 接触的变化和基因的表达。我们观察到，在未经处理和分化的 K562 细胞中，大约有 200 对 rDNA 接触基因以不同的组合共同表达。rDNA 接触在分化过程中发生变化，并与基因的上调表达相关联，这些基因的产物主要位于核内，并且与 DNA 和 RNA 结合高度相关，同时与基因的下调表达相关联，这些基因的产物主要位于细胞质或细胞内或细胞外小泡中。下调最明显的基因是 ，它是分化的抑制剂，因此应该关闭以允许分化。我们的数据表明，K562 细胞的分化导致 rDNA 簇的染色体间接触和特定染色体区域的 3D 结构发生改变，以及位于相应染色体区域的基因表达发生变化。我们得出结论，大约一半的 rDNA 接触基因在人类细胞中共同表达，并且 rDNA 簇参与基因表达的全局调控。
