differential roles for the E2A activation domains in B lymphocytes and macrophages.
The E2A gene encodes two E protein/class I basic helix-loop-helix transcription factors, E12 and E47, that are essential for B lymphopoiesis. In addition to the DNA-binding and protein dimerization domain, the E proteins share two highly conserved transcription activation domains. In this study, we show that both activation domains are required for optimal E2A-dependent transcription. Surprisingly, however, neither activation domain is required for E2A to rescue B lymphopoiesis from E2A(-/-) hemopoietic progenitors, although the N terminus of E2A, which harbors some transcription capacity, is required. Therefore, the E protein activation domains function redundantly in promoting B cell development. In contrast, the N-terminal activation domain, AD1, is required for a newly described ability of E2A to suppress macrophage development in vitro. Our findings demonstrate distinct functionalities for the E protein activation domains in B lymphocytes and macrophages.
Bhalla
Savita
S
Department of Pathology, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Spaulding
Christina
C
Brumbaugh
Rachel L
RL
Zagort
Derek E
DE
Massari
Mark E
ME
Murre
Cornelis
C
Kee
Barbara L
BL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D039481:CD11b Antigen / Q000032:analysis; D008213:Lymphocyte Activation / Q000235:genetics*; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000502:physiology; D015533:Transcriptional Activation
D051792:Basic Helix-Loop-Helix Proteins; D039481:CD11b Antigen; C075668:Tcf3 protein, mouse