Induction of the Erythroid Differentiation of K562 Cells Is Coupled with Changes in the Inter-Chromosomal Contacts of rDNA Clusters

Abstract

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 Drosophila 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 ID3, 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.

Asperuloside regulates the proliferation, apoptosis, and differentiation of chronic myeloid leukemia cell line K562 through the RAS/MEK/ERK pathway

“…The production of erythrocytes is a complex process, and once the development of erythroid cells stops at a certain stage and eventually fails to differentiate into mature erythrocytes, will lead to a variety of diseases, among which leukemia is the most serious and common one [ 28 , 29 ]. K562 cell line was first isolated from the pleural effusion of patients with CML in blast crisis [ 16 ]. The P210 protein produced by the BCR-ABL fusion gene in K562 cells significantly increased the activity of tyrosine kinase, resulting in enhanced malignant behavior of cells [ 30 , 31 ].…”

“…Inhibiting the proliferation of malignant cells and promoting their normal differentiation is the focus of the current treatment of hematological malignancies [ 15 ]. K562, a cell line isolated from CML patients, has the characteristics of stem cells and is more similar to undifferentiated early multipotent hematopoietic progenitor cells in behavior [ 16 ]. It is an ideal model for inducing cell differentiation [ 17 ].…”

Preferential Co-Expression and Colocalization of rDNA-Contacting Genes with LincRNAs Suggest Their Involvement in Shaping Inter-Chromosomal Interactions with Nucleoli

“…Recently, it was reported that during differentiation, changes in rDNA–genomic contacts are coupled with changes in the 3D nets of chromosomal structures around developmental genes [ 6 ]. These alterations in the inter-chromosomal contacts of rDNA clusters and 3D structures in particular chromosomal regions lead to changes in the expression of genes located in the corresponding chromosomal domains [ 7 ]. About half of the rDNA-contacting genes are co-expressed in human cells [ 7 ].…”

“…These alterations in the inter-chromosomal contacts of rDNA clusters and 3D structures in particular chromosomal regions lead to changes in the expression of genes located in the corresponding chromosomal domains [ 7 ]. About half of the rDNA-contacting genes are co-expressed in human cells [ 7 ]. Taken together, these data suggest that 3D structures shaped by rDNA clusters are involved in the global regulation of gene expression [ 7 ].…”

“…About half of the rDNA-contacting genes are co-expressed in human cells [ 7 ]. Taken together, these data suggest that 3D structures shaped by rDNA clusters are involved in the global regulation of gene expression [ 7 ].…”