The regulatory interplay between Oct-1 isoforms contributes to hematopoiesis and the isoforms imbalance correlates with a malignant transformation of B cells.

Elizaveta V Pankratova,Sofia G Georgieva,Irina D Krylova,Tatiana N Portseva,Alexander G Stepchenko

doi:10.18632/oncotarget.25648

Abstract

Oct-1(POU2F1) is a DNA-binding transcription regulator and its level being highly increased in many human cancers. Oct-1 is present in the human cells as a family of functionally different isoforms which are transcribed from alternative promoters. Here, we have demonstrated that expression patterns of Oct-1 isoforms change during differentiation of hematopoetic progenitor cells (CD34+) (HPCs) to the B (CD19+) and T (CD3+) cells. While Oct-1L is expressed at a high level in the CD34+ HPCs, its expression level drops dramatically during the T-cell differentiation, although remains nearly the same in B-cells. We have described the novel human Oct-1R isoform which is conserved in mammals and is B cell-specific. Oct-1R was found in B cells, but not in HPCs. Oct-1R is transcribed from the same promoter as Oct-1L, another lymphocyte-specific isoform. Overexpression of Oct-1R and Oct-1L in the Namalwa cells leads to the repression of many genes involved in B-lymphocyte differentiation and signal transduction. Thus these isoforms may regulate the particular stages of development of normal B cells and maintain their proper differentiation status. However the extremely high level of Oct-1L isoform observed in the B-lymphoblast tumor cell lines indicated that the excess of Oct-L seem likely to considerably decrease the differentiation ability of these cells. Oct-1 may serve as a therapeutic target for many tumors, but it should be noted that in a tumor the content of a certain isoform Oct-1, rather than the total Oct-1 protein, can be increased.

Highlights

Oct-1(POU2F1), the member of the group of DNA-binding transcription regulators of higher eukaryotes, controls a wide range of targets including the housekeeping genes and genes specific for immune, endocrine, and nervous systems [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]
We have described the novel human Oct-1R isoform which is conserved in mammals and is B cell-specific
The transcript starts at the tissue-specific L promoter and the resulting Oct-1R isoform shares the N-terminal sequences and the intact POU domain with Oct-1L, while lacking 132 amino acid residues at the C-terminus due to the incorporation of the alternative exon 23a containing a stop codon (Figure 1A)

Summary

Introduction

Oct-1(POU2F1), the member of the group of DNA-binding transcription regulators of higher eukaryotes, controls a wide range of targets including the housekeeping genes and genes specific for immune, endocrine, and nervous systems [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. Oct-1 controls the expression of a considerable number of tissue-specific genes It plays a significant role in the immune system development and function being the expression regulator of the IL2 [8], IL8 [9], IL3, and IL5 interleukin genes, GCSF gene [13], mb-1 [11] and B29 [12], Ly9 [13], and the genes encoding light and heavy immunoglobulin chains [14]. Oct-1 is essential for the control of apoptosis [24,25,26] and glycolytic metabolism [24, 27]

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Conclusion