c-FMS chromatin structure and expression in normal and leukaemic myelopoiesis.
The macrophage colony-stimulating factor receptor is encoded by the c-FMS gene, and it has been suggested that altered regulation of c-FMS expression may contribute to leukaemic transformation. c-FMS is expressed in pluripotent haemopoietic precursor cells and is subsequently upregulated during monocytic differentiation, but downregulated during granulopoiesis. We have examined transcription factor occupancy and aspects of chromatin structure of the critical c-FMS regulatory element located within the second intron (FIRE - fms intonic regulatory element) during normal and leukaemic myelopoiesis. Granulocytic differentiation from normal and leukaemic precursors is accompanied by loss of transcription factors at FIRE and downregulated c-FMS expression. The presence of AML1-ETO in leukaemic cells does not prevent this disassembly. In nonleukaemic cells, granulocytic differentiation is accompanied by reversal to a chromatin fine structure characteristic of c-FMS-nonexpressing cells. In addition, we show that low-level expression of the gene in leukaemic blast cells and granulocytes does not associate with increased CpG methylation across the c-FMS locus.
Follows
George Alexander
GA
Molecular Medicine Unit, St James's University Hospital, Leeds, UK. gf246@cam.ac.uk
Tagoh
Hiromi
H
Richards
Stephen John
SJ
Melnik
Svitlana
S
Dickinson
Helen
H
de Wynter
Erica
E
Lefevre
Pascal
P
Morgan
Gareth John
GJ
Bonifer
Constanze
C
D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002843:Chromatin / Q000737:chemistry / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology*; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data; D038042:Myelopoiesis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
D002843:Chromatin; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D016186:Receptor, Macrophage Colony-Stimulating Factor