Gene rearrangement patterning and DNase-I hypersensitive sites within the T-cell receptor J alpha locus.
For several years, the relationship between alpha beta and gamma delta T-cell progenitors has been a topic of debate. Some argue that a subset of T-cell progenitors is "pre-committed" to the alpha beta lineage and is thus programmed to rearrange alpha, but not delta genes. It is further argued that the deletion of the delta locus by a unique rearrangement, delta rec-psi J alpha, may be the critical forerunner to V-J alpha joins in alpha beta committed cells and that a hypersensitive site (HS) termed 5'TEA might regulate such rearrangement. Here we present an alternative hypothesis. We first emphasize that directed J alpha gene rearrangements do not exclusively target the psi J alpha gene, but that clustered gene rearrangements occur throughout the J alpha locus during T-cell development. We describe the existence of not one, but at least two HS sites distributed along the J alpha locus which might serve as regulators for the gene rearrangement event. Finally, we suggest that progenitor T-cells are not committed to a particular delta or alpha gene rearrangement, but that a flexible progenitor responds to complex interactions between environmental signals and multiple regulatory elements interspersed among delta/alpha genes.
Dave
V P
VP
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38101.
Hurwitz
J L
JL
D000818:Animals; D015139:Blotting, Southern; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D003850:Deoxyribonuclease I / Q000378:metabolism; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D015183:Restriction Mapping; D013601:T-Lymphocytes
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D003850:Deoxyribonuclease I