Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A.
The basic helix-loop-helix transcription factors encoded by the E2A gene function at the apex of a transcriptional hierarchy involving E2A, early B cell factor (EBF), and Pax5, which is essential for B lymphopoiesis. In committed B lineage progenitors, E2A proteins have also been shown to regulate many lineage-associated genes. Herein, we demonstrate that the block in B lymphopoiesis imposed by the absence of E2A can be overcome by expression of EBF, but not Pax5, indicating that EBF is the essential target of E2A required for development of B lineage progenitors. Our data demonstrate that EBF, in synergy with low levels of alternative E2A-related proteins (E proteins), is sufficient to promote expression of most B lineage genes. Remarkably, however, we find that E2A proteins are required for interleukin 7-dependent proliferation due, in part, to a role for E2A in optimal expression of N-myc. Therefore, high levels of E protein activity are essential for the activation of EBF and N-myc, whereas lower levels of E protein activity, in synergy with other B lineage transcription factors, are sufficient for expression of most B lineage genes.
Seet
Christopher S
CS
Department of Pathology, University of Chicago, 5841 S. Maryland Avenue, MC 1089, Chicago, IL 60637, USA.
Brumbaugh
Rachel L
RL
Kee
Barbara L
BL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D016259:Genes, myc; D018257:Helix-Loop-Helix Motifs / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology*; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D015851:Interleukin-7; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors