E47 is required for V(D)J recombinase activity in common lymphoid progenitors

J Exp Med. 2005 Dec 19;202(12):1669-77. doi: 10.1084/jem.20051190.

Abstract

Common lymphoid progenitors (CLPs) are the first bone marrow precursors in which V(D)J recombinase activity is up-regulated. Here, we show that loss of the transcription factor E47 produces a reduced CLP population that lacks V(D)J recombinase activity and D-J(H) rearrangements in vivo. Apart from a profound arrest before the pro-B cell stage, other downstream lymphoid progeny of CLPs are still intact in these mice albeit at reduced numbers. In contrast to the inhibition of recombinase activity in early B lineage precursors in E47-deficient animals, loss of either E47 or its cis-acting target Erag (enhancer of rag transcription) has little effect on recombinase activity in thymic T lineage precursors. Taken together, this work defines a role for E47 in regulating lineage progression at the CLP stage in vivo and describes the first transcription factor required for lineage-specific recombinase activity.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • Cell Lineage / physiology*
  • DNA Primers
  • Flow Cytometry
  • Gene Expression Regulation, Enzymologic*
  • Gene Rearrangement, B-Lymphocyte / genetics*
  • Gene Rearrangement, B-Lymphocyte / physiology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Polymerase Chain Reaction
  • TCF Transcription Factors / metabolism*
  • Transcription Factor 7-Like 1 Protein
  • VDJ Recombinases / metabolism*

Substances

  • DNA Primers
  • Homeodomain Proteins
  • TCF Transcription Factors
  • Tcf7l1 protein, mouse
  • Transcription Factor 7-Like 1 Protein
  • RAG-1 protein
  • VDJ Recombinases