E47 is required for V(D)J recombinase activity in common lymphoid progenitors.
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.
Borghesi
Lisa
L
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. borghesi@pitt.edu
Aites
Jennifer
J
Nelson
Shakira
S
Lefterov
Preslav
P
James
Pamela
P
Gerstein
Rachel
R
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D019070:Cell Lineage / Q000502:physiology*; D017931:DNA Primers; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D051820:TCF Transcription Factors / Q000378:metabolism*; D058125:Transcription Factor 7-Like 1 Protein; D045567:VDJ Recombinases / Q000378:metabolism*
D017931:DNA Primers; D018398:Homeodomain Proteins; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; C064658:RAG-1 protein; D045567:VDJ Recombinases