Linked Life Data

20554963

Source:http://linkedlifedata.com/resource/pubmed/id/20554963

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-7-5
pubmed:abstractText
The B cell-activating factor of the TNF family receptor (BAFF-R), encoded by the TNFRSF13C gene, is critically important for transitional B cell survival to maturity. Thus, ligation of BAFF-R by BAFF delivers a potent survival signal. Reports implicating the BAFF/BAFF-R signaling axis in the pathogenesis of autoimmune human diseases and B lineage malignancies have largely prompted studies focusing on BAFF expression; however, there is an equally critical need to better understand BAFF-R expression. Initial BAFF-R expression, although characterized in murine B cells, has not yet been reported in human B lymphopoiesis. In this study, we first demonstrate that BAFF-R expression is absent from early precursors and is acquired by bone marrow B cells newly expressing the BCR. We next focused on identifying the specific genomic region that controls BAFF-R expression in mature B cells (i.e., the TNFRSF13C promoter). To accomplish this, we used in silico tools examining interspecies genomic conservation in conjunction with reporter constructs transfected into malignant B and plasma cell lines. DNase protection assays using nuclear extracts from BAFF-R-expressing cells suggested potential regulatory sites, which allowed the generation of EMSA probes that bound NFs specific to BAFF-R-expressing cells. With a more stringent analysis of interspecies homology, these assays identified a site at which a single nucleotide substitution could distinctly impact promoter activity. Finally, chromatin immunoprecipitation assays revealed the in vivo binding of the specific transcription factor c-Rel to the most proximal genomic region, and c-Rel small interfering RNA transfections in BAFF-R-expressing lines demonstrated a coincident knockdown of both c-Rel and BAFF-R mRNA.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
185
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1045-54
pubmed:dateRevised
2010-11-16
pubmed:meshHeading
pubmed-meshheading:20554963-Animals, pubmed-meshheading:20554963-B-Cell Activation Factor Receptor, pubmed-meshheading:20554963-B-Lymphocytes, pubmed-meshheading:20554963-Binding Sites, pubmed-meshheading:20554963-Cell Differentiation, pubmed-meshheading:20554963-Cell Line, pubmed-meshheading:20554963-Cell Line, Tumor, pubmed-meshheading:20554963-Chromatin Immunoprecipitation, pubmed-meshheading:20554963-Chromosome Mapping, pubmed-meshheading:20554963-Computational Biology, pubmed-meshheading:20554963-Electrophoretic Mobility Shift Assay, pubmed-meshheading:20554963-Gene Expression Profiling, pubmed-meshheading:20554963-Humans, pubmed-meshheading:20554963-Immunoblotting, pubmed-meshheading:20554963-Luciferases, pubmed-meshheading:20554963-Mice, pubmed-meshheading:20554963-Point Mutation, pubmed-meshheading:20554963-Promoter Regions, Genetic, pubmed-meshheading:20554963-Proto-Oncogene Proteins c-rel, pubmed-meshheading:20554963-RNA Interference, pubmed-meshheading:20554963-Recombinant Fusion Proteins, pubmed-meshheading:20554963-Synteny, pubmed-meshheading:20554963-Transcription Factors, pubmed-meshheading:20554963-Transfection
pubmed:year
2010
pubmed:articleTitle
The structure of the TNFRSF13C promoter enables differential expression of BAFF-R during B cell ontogeny and terminal differentiation.
pubmed:affiliation
Department of Immunology, Mayo Graduate School, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural