CTCF transcriptional regulator: role in the hematopoietic differentiation

Abstract

The transcriptional regulator CTCF is an important chromatin organizer and epigenetic regulator of genes involved in cancer. Previous results of our group reported that CTCF is differentially regulated during the hematopoietic differentiation of human leukemia cells. Overexpression of CTCF inhibits proliferation and induces erythroid differentiation by inducing some erythroid genes and repressing undifferentiation genes. In this study we aimed to investigate the consequences of CTCF down-regulation in the erythroid differentiation using both leukemia cell lines and primary CD34+ hematopoietic stem cells. A human cell line, K562 that can be chemically induced to differentiate into various hematopoietic lineages, was chosen as a model system. To induce erythroid differentiation, K562 cells were treated with 1--Darabinofuranosylcytosine (Ara-C). Lentiviral particles carrying short hairpin against CTCF were produced for silencing CTCF in K562 cell, as well as in CD34+ cells. By using this model system we demonstrated that: i) shCTCF lentiviral particles are able to silence the expression of CTCF in K562 cells; ii) CTCF down-regulation inhibits the erythroid differentiation upon AraC treatment; iii) CTCF down-regulation represses the erythroid differentiation by repressing the expression of some erythroid genes iv) we purified CD34+cells from cord blood and infected them with lentiviral particles to silence CTCF. All of these results lead us to suggest that CTCF has an important role in the control of erythroid differentiation.