CTCF regulates growth and erythroid differentiation of human myeloid leukemia cells.
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.
Torrano
Verónica
V
Grupo de Biología Molecular del Cáncer, Departamento de Biologia Molecular, Unidad de Biomedicina-CSIC, Universidad de Cantabria, 39011 Santander, Spain.
Chernukhin
Igor
I
Docquier
France
F
D'Arcy
Vivien
V
León
Javier
J
Klenova
Elena
E
Delgado
M Dolores
MD
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection; D016335:Zinc Fingers
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D012097:Repressor Proteins; D003570:Cytidine Triphosphate; C038673:5-aza-2'-deoxycytidine-5'-triphosphate; D001374:Azacitidine