A role for E2-2 at the DN3 stage of early thymopoiesis.
Roles for the E-proteins E2A and HEB during T lymphocyte development have been well established. Based on our previous observations of counter selection against T cells lacking E2-2, it seemed reasonable to assume that there would be a function also for E2-2 in thymocyte development. Aiming at assigning such a role for E2-2, we analyzed the expression of E2-2, E2A, HEB as well as Id mRNA during T cell development. Interestingly, whereas all three E-proteins were expressed during early thymocyte development, significant expression beyond the DP stage was detected only for E2A. Among the Id proteins, Id2 displayed a prominent expression exclusively in DN1, whereas Id3 showed some expression in DN1, followed by a down regulation and then a prominent induction, peaking in the DP stage. E2-2 was expressed during the DN stages, as well as in the DP stage, suggesting that E2-2 operates in concert with the other E-proteins during early thymocyte development. We found that E2-2 null thymocytes displayed a partial block at the DN3 stage of development, as well as a reduced expression of pre-T alpha, known to be regulated also by E2A and HEB. The fact that E2-2 deficient thymocytes develop without gross abnormalities is likely to stem from redundancy due to the co-expression of E2A and HEB.
Wikström
Ingela
I
Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, 901 85 Umeå, Sweden.
Forssell
Johan
J
Penha-Goncalves
Mario N
MN
Bergqvist
Ingela
I
Holmberg
Dan
D
D000818:Animals; D017209:Apoptosis; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005333:Fetus / Q000166:cytology; D005786:Gene Expression Regulation; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D051820:TCF Transcription Factors / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*; D000073940:Transcription Factor 4; D014158:Transcription, Genetic
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D051796:Inhibitor of Differentiation Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051820:TCF Transcription Factors; D000073940:Transcription Factor 4; C489532:Tcf12 protein, mouse; C075668:Tcf3 protein, mouse; C090743:Tcf4 protein, mouse; C090377:pre-T cell receptor alpha