Immunoglobulin heavy-chain and CD3 delta-chain gene enhancers are DNase I-hypersensitive in hemopoietic progenitor cells.
Multipotential interleukin 3-dependent non-immortalized murine hemopoietic progenitor cells have DNase I-hypersensitive sites in the immunoglobulin heavy-chain and CD3 delta enhancers and transcribe germ-line T-cell antigen receptor gamma-chain (TCR gamma), but not IgM or TCR beta, genes. Induction of myeloid differentiation in these cells clones down expression and/or transcriptional accessibility of the immunoglobulin heavy-chain and TCR gamma genes. The CD3 delta enhancer region remains DNase I-hypersensitive but closes down in B cells. In embryonic stem cells and pan-mesodermal cells, these genes or enhancer regions are neither expressed nor DNase I-hypersensitive. These data suggest that lineage potential may be programmed, at least in part, by alterations in the accessibility or conformation of regulatory regions of genes and that some promiscuity of gene expression and/or accessibility can precede lineage commitment and maturation in progenitor cells induced to self-renew by interleukin 3.
Ford
A M
AM
Leukaemia Research Fund Centre, Chester Beatty Laboratories, London, United Kingdom.
Bennett
C A
CA
Healy
L E
LE
Navarro
E
E
Spooncer
E
E
Greaves
M F
MF
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001853:Bone Marrow / Q000276:immunology; D017252:CD3 Complex; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D005803:Genes, Immunoglobulin; D006098:Granulocytes / Q000276:immunology; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007377:Interleukin-3 / Q000494:pharmacology; D008745:Methylation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D006133:Growth Substances; D007143:Immunoglobulin Heavy Chains; D007377:Interleukin-3; D011948:Receptors, Antigen, T-Cell; D003850:Deoxyribonuclease I