NF-HB (BSAP) is a repressor of the murine immunoglobulin heavy-chain 3' alpha enhancer at early stages of B-cell differentiation.

Singh, Mallika; Birshtein, Barbara K.

doi:10.1128/mcb.13.6.3611

Cited by 132 publications

(108 citation statements)

References 46 publications

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“…Its action is bimodal: for example, it regulates transcription from the CD19 promoter positively, but acts negatively in the context of the IgH 3' enhancer (Singh and Birshtein, 1993;Neurath et al, 1994;Pettersson et al, 1997;Nutt et al, 1998;Maitra and Atchison, 2000). We used RNase protection mapping to assess expression levels of the PAX-5 gene in HRS cell lines relative to levels in Daudi cells (Figure 2c).…”

Section: Resultsmentioning

confidence: 99%

“…Intronic and 3' enhancers of both IgH and Ig k light chain genes contain multiple elements of the E-box class, mutation of any of which significantly reduces enhancer activity (reviewed in Lieberman and Singh and Birshtein, 1993;Neurath et al, 1994). E12 and E47, that are different splicing products of the E2A gene bind these sites in B cells, although homodimers of E47 appear to be the predominant transcriptionally active form (Bain et al, 1993;Shen and Kadesch, 1995).…”

Section: Resultsmentioning

confidence: 99%

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Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

et al. 2002

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In classical Hodgkin lymphoma the malignant Hodgkin/ Reed-Sternberg (HRS) cells characteristically constitute only a small minority of the tumour load. Their origin has been debated for decades, but on the basis of rearrangement and somatic hypermutations of their immunoglubulin (Ig) genes, HRS cells are now ascribed to the B-cell lineage. Nevertheless, phenotypically HRS cells have lost their B cell identity: they usually lack common B cell-specific surface markers such as CD19 and CD79a as well as Ig gene transcripts. Here we demonstrate that Ig promoters as well as both intronic and 3' enhancer sequences are transcriptionally inactive in HRS cell lines. This inactivity correlates with either reduced levels or even a complete lack of several B cellspecific transcription factors required for their expression: Oct-2, OBF-1, PU.1, E47/E12, PAX-5 and EBF. Moreover, we demonstrate that PU.1 and PAX-5 are significantly down-regulated in HRS cells in pathological specimens from primary tumour tissues. However, forced expression of these transcription factors can activate regulatory sequences of silenced B cell marker genes, and in one instance also transcription from a silenced endogenous locus. Thus, HRS cells are dedifferentiated B cells with global down-regulation of B cell-specific genes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

et al. 2002

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“…BSAP (Pax5) has been implicated in the regulation of several B-cell-specific genes primarily based on the identification of BSAP-binding sites in their control regions. Putative BSAP targets are the le pro moter (Liao et al 1994) and 3' enhancers of the IgH and IgL^ loci (Singh and Birshtein 1993;Neurath et al 1994;Roque et al 1996) as well as the genes coding for the cell surface protein CD19 , the tyrosine kinase Blk (Zwollo and Desiderio 1994), the transcrip tion factor XBP-1 (Reimold et al 1996), and the surrogate light chains \5 and VpreBl (Okabe et al 1992).…”

mentioning

confidence: 99%

Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus.

Nutt¹,

Urbánek²,

Rolink³

et al. 1997

Genes Dev.

378

377

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“…1 In vitro experiments using mobility shift assays have shown that several B-cell-specific genes contain BSAP-binding sites, including the CD19 (4, 7), CD20 (8), V pre-B , 5 (9), and blk (10) promoters, as well as IgH chain switch regions (11) and the Ig 3Ј␣ (12) enhancer. These results are somewhat in contrast with in vivo data from Pax-5 null mice (which lack BSAP) because, although pro-B-cells isolated from these mice no longer express CD19 (as would be expected), blk, V pre-B , and 5 genes are still expressed at wild-type levels (13).…”

mentioning

confidence: 99%

The Pax-5 Gene Is Alternatively Spliced during B-cell Development

Zwollo

Arrieta

Ede

et al. 1997

Journal of Biological Chemistry

114

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The transcription factor Pax-5 is expressed during the early stages of B-cell differentiation and influences the expression of several B-cell-specific genes. In addition to the existing isoform (Pax-5, which we have named Pax5a), we have isolated three new isoforms, Pax-5b, Pax5d, and Pax-5e, from murine spleen and B-lymphoid cell lines using library screenings and polymerase chain reaction amplification. Isoforms Pax-5b and Pax-5e have spliced out their second exon, resulting in proteins with only a partial DNA-binding domain. Isoforms Pax-5d and Pax-5e have deleted the 3 -region, which encodes the transactivating domain, and replaced it with a novel sequence. The existence of alternative Pax-5 transcripts was confirmed using RNase protection assays. Furthermore, Pax-5a and Pax-5b proteins were detected using Western blot analysis. Pax-5a was detectable in pro-, pre-, and mature B-cell lines, but not in two plasmacytomas; Pax-5b was shown to be present at low levels in mature B-cell lines and, unexpectedly, in one plasma cell line, but not in pro-B-cell or T-cell lines. Mobility shift assays showed that in vitro translated Pax-5a and Pax5d, but not Pax-5b or Pax-5e, could interact with a B-cellspecific activator protein-binding site on the blk promoter. Using this assay, we also showed that Pax-5d was present in nuclear extracts of some (but not all) B-lymphoid lines and interacts with the B-cell-specific activator protein-binding site. The pattern of differential expression of alternatively spliced Pax-5 isoforms suggests that they may be important regulators of transcription during B-cell maturation.Development of multicellular organisms involves highly regulated expression of specific transcription factors that direct cells into their proper differentiation pathways through interactions with specific target genes. Typically, transcription factors are divided into groups on the basis of the structural and functional similarity of their DNA-binding domains, such as the basic leucine zipper, basic helix-loop-helix, zinc finger, and homeobox families. One small family of transcription factors involved in development is the paired box (Pax) gene family, containing at least nine members, Pax-1 through Pax-9 (1, 2). All members contain a conserved DNA-binding domain encoding the paired box, which consists of a 128-amino acid sequence at the amino-terminal side of the protein. Other conserved regions in Pax proteins include an octamer and a homeodomain sequence in the center of the protein and a transactivating domain that spans 100 amino acids in the Ser/Thr/Pro-rich region at the carboxyl-terminal end (3, 4).Pax genes are grouped into four classes based on structural similarity (5). Class I contains Pax-1 and Pax-9, which lack a homeodomain. Two Class II members, Pax-3 and Pax-7, encode both an octamer and a complete homeodomain. Class III, which includes Pax-2, Pax-5, and Pax-8, represents the class of Pax genes containing an octamer sequence as well as an incomplete homeodomain. Finally, Class IV contains Pax-4 ...

show abstract

NF-HB (BSAP) is a repressor of the murine immunoglobulin heavy-chain 3' alpha enhancer at early stages of B-cell differentiation.

Cited by 132 publications

References 46 publications

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus.

The Pax-5 Gene Is Alternatively Spliced during B-cell Development

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