Regulation of E2A gene expression in B-lymphocyte development.
Biochemical and genetic studies have demonstrated that transcription factors encoded by the E2A gene are essential in regulating B lineage specific gene expression and B lineage commitment. However, the mechanism by which E2A regulates B lineage commitment is not known. It has been reported that E2A controls B lineage commitment in a dosage dependent manner. To further investigate this gene dosage effect, we analyzed E2A expression during normal B cell development in mice carrying a functional E2AGFP knockin allele. Mice carrying this fusion allele were examined for E2A gene expression during bone marrow B cell development. A dramatic upregulation of E2A is observed concomitant with the initiation of immunoglobulin heavy chain D-J rearrangement and the induction of Early B cell Factor (EBF) gene expression. We also show that this E2A upregulation does not occur in the absence of the EBF gene. These results indicate that E2A upregulation is a critical step in regulating B-lineage commitment. It further suggests that E2A gene dosage may be determined by a cross regulation between E2A and EBF during B lineage commitment.
Zhuang
Yuan
Y
Department of Immunology, Duke University Medical Center, Jones Building Room 329, Box 3010, Durham, NC 27710, USA. yzhuang@duke.edu
Jackson
Annette
A
Pan
Lihua
L
Shen
Kang
K
Dai
Meifang
M
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002472:Cell Transformation, Viral; D018628:Gene Dosage; D005786:Gene Expression Regulation; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics / Q000276:immunology; D018390:Gene Targeting; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006720:Homozygote; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D014157:Transcription Factors