title: differential roles for the E2A activation domains in B lymphocytes and macrophages.
abstract: 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.
authors.affiliation: Department of Pathology, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Savita
authors.initials: S
authors.lastname: Bhalla
authors.forename: Christina
authors.initials: C
authors.lastname: Spaulding
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Brumbaugh
authors.forename: Derek E
authors.initials: DE
authors.lastname: Zagort
authors.forename: Mark E
authors.initials: ME
authors.lastname: Massari
authors.forename: Cornelis
authors.initials: C
authors.lastname: Murre
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Kee
mesh_terms: 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
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D039481:CD11b Antigen; C075668:Tcf3 protein, mouse