Early Thymocyte Development Is Regulated by Modulation of E2a Protein Activity

• DOI: 10.1084/jem.194.6.733
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Isaac Engel; Carol Johns; Gretchen Bain; Richard R. Rivera; Cornelis Murre
• Keywords: Thymocyte; Basic helix-loop-helix

The E2A gene encodes the E47 and E12 basic helix-loop-helix (bHLH) transcription factors. T cell development in E2A-deficient mice is partially arrested before lineage commitment. Here we demonstrate that expression becomes uniformly high at point which thymocytes begin to commit towards lineage. protein levels remain until double positive developmental stage, they drop relatively moderate levels, are further downregulated upon transition single stage. However, stimuli mimic pre-T receptor (TCR) signaling committed precursors inhibit DNA-binding activity induce bHLH inhibitor Id3 through a mitogen-activated kinase kinase-dependent pathway. Consistent with these observations, deficiency proteins completely abrogates block observed defects TCR rearrangement. Thus necessary for both initiating differentiation inhibiting absence of pre-TCR expression. Mechanistically, data link mediated downstream target genes into common