Transcription Factor Pax5 Activates the Chromatin of Key Genes Involved in B Cell Signaling, Adhesion, Migration, and Immune Function
Autor: | Shane McManus, Giorgia Salvagiotto, Alessio Delogu, Alexandra Schebesta, Georg A. Busslinger, Meinrad Busslinger |
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Rok vydání: | 2007 |
Předmět: |
TBX1
Immunology Biology Mice immune system diseases Cell Movement hemic and lymphatic diseases Cell Adhesion Animals Immunology and Allergy Enhancer MOLIMMUNO ChIA-PET Locus control region Cells Cultured Oligonucleotide Array Sequence Analysis Mice Knockout B-Lymphocytes Gene Expression Profiling Stem Cells PAX5 Transcription Factor Promoter Cell Differentiation Molecular biology Fusion protein Chromatin Mice Inbred C57BL Infectious Diseases Chromatin immunoprecipitation Signal Transduction |
Zdroj: | Immunity. 27(1):49-63 |
ISSN: | 1074-7613 |
DOI: | 10.1016/j.immuni.2007.05.019 |
Popis: | SummaryThe transcription factor Pax5 represses B lineage-inappropriate genes and activates B cell-specific genes in B lymphocytes. Here we have identified 170 Pax5-activated genes. Conditional mutagenesis demonstrated that the Pax5-regulated genes require continuous Pax5 activity for normal expression in pro-B and mature B cells. Expression of half of the Pax5-activated genes is either absent or substantially reduced upon Pax5 loss in plasma cells. Direct Pax5 target genes were identified based on their protein synthesis-independent activation by a Pax5-estrogen receptor fusion protein. Chromatin immunoprecipitation (ChIP) of Pax5 together with chromatin profiling by ChIP-on-chip analysis demonstrated that Pax5 directly activates the chromatin at promoters or putative enhancers of Pax5 target genes. The Pax5-activated genes code for key regulatory and structural proteins involved in B cell signaling, adhesion, migration, antigen presentation, and germinal-center B cell formation, thus revealing a complex regulatory network that is activated by Pax5 to control B cell development and function. |
Databáze: | OpenAIRE |
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