CTCF Regulates Growth and Erythroid Differentiation of Human Myeloid Leukemia Cells

M Dolores Delgado,Verónica Torrano,Vivien D'Arcy,Javier León,Igor Chernukhin,France Docquier,Elena Klenova

doi:10.1074/jbc.m501481200

M Dolores Delgado, Verónica Torrano + Show 5 more

Open Access

https://doi.org/10.1074/jbc.m501481200

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Abstract

CTCF is a transcription factor and a candidate tumor suppressor that contains a DNA-binding domain composed of 11 zinc fingers. We reported previously that CTCF is differentially regulated during differentiation of human myeloid leukemia cells. In this study we aimed to investigate the role of CTCF in myeloid cell differentiation. A human cell line, K562, that can be chemically induced to differentiate into various hematopoietic lineages was chosen as a model system for this study. Several K562 cell lines with constitutive and conditional expression of CTCF have been generated. By using these model systems we demonstrated that: (i) ectopic expression of CTCF in K562 cells led to growth retardation and promotion of differentiation into the erythroid lineage; (ii) CTCF knock-down significantly inhibited differentiation of K562 cells into erythroid lineage; (iii) differentiation of K562 into the megakaryocytic lineage was not significantly affected; and (iv) down-regulation of MYC has been identified as one of the mechanisms by which CTCF promotes erythroid differentiation. Taken together our results demonstrate that CTCF is involved in the control of myeloid cell growth and differentiation.

Highlights

CTCF is a transcription factor, which contains a DNA-binding domain composed of 11 zinc fingers [1, 2]
Inhibition of CTCF Expression with the Antisense ODN Enhances Proliferation of K562 Cells—We previously demonstrated that CTCF is differentially expressed and post-translationally modified, depending on the differentiation lineage of human myeloid cells [26]
A notable reduction of CTCF was observed in K562 cells exposed to antisense AS1 or AS6 for 3 days, compared with the untreated cells or cells treated with sense S1 and S6 ODN (Fig. 1B and data not shown)

Summary

Introduction

CTCF is a transcription factor, which contains a DNA-binding domain composed of 11 zinc fingers [1, 2]. Human cell lines derived from myeloid leukemias have been widely used as models to study the molecular control of hematopoietic cell proliferation and differentiation. They can be induced into erythroid, megakaryocytic, monocytic-macrophagic, or granulocytic lineages in response to specific differentiation inducers [25]. CTCF expression and post-translational modification of CTCF during differentiation of several human myeloid cells, such as K562, HL60, U937, and THP1 into different lineages have been investigated in our previous studies [26]. We found that CTCF was differentially expressed and post-translationally modified depending on the particular differentiation pathway These results indicated that CTCF may be important in the regulation of growth and differentiation in human myeloid cells. K562 can be differentiated into the erythroid lineage with cytosine arabinoside (Ara-C)

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