The regulation of the B-cell gene expression programme by Pax5.
The activity of the transcription factor paired box gene 5 (Pax5) is essential for many aspects of B lymphopoiesis including the initial commitment to the lineage, immunoglobulin rearrangement, pre-B cell receptor signalling and maintaining cell identity in mature B cells. Deregulated or reduced Pax5 activity has also been implicated in B-cell malignancies both in human disease and mouse models. Candidate gene approaches and biochemical analysis have revealed that Pax5 regulates B lymphopoiesis by concurrently activating B cell-specific gene expression as well as repressing the expression of genes, many of which are associated with non-B cell lineages. These studies have been recently complemented with more exhaustive microarray studies, which have identified and validated a large panel of Pax5 target genes. These target genes reveal a gene regulatory network, with Pax5 at its centre that controls the B-cell gene expression programme.
Holmes
Melissa L
ML
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Pridans
Clare
C
Nutt
Stephen L
SL
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019070:Cell Lineage / Q000276:immunology; D015536:Down-Regulation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000276:immunology
C497762:Notch1 protein, mouse; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D051881:Receptor, Notch1; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3