SPI-C, a PU-box binding ETS protein expressed temporarily during B-cell development and in macrophages, contains an acidic transactivation domain located to the N-terminus

Carlsson, Robert; Persson, C.; Leanderson, Tomas

doi:10.1016/s0161-5890(03)00032-4

Cited by 17 publications

(21 citation statements)

References 31 publications

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“…Spi-C has an extremely restricted pattern of expression: its transcription is initiated at the pre-B cell stage of B cell development, it is expressed in mature B cells, and its transcription is extinguished in plasma cells (16,17). Taken together, these results suggest that the normal function of Spi-C might be as a negative regulator of PU.1/Spi-B activity (17,65). We speculate that Spi-C may normally interfere with PU.1/Spi-B activity starting at the large pre-B cell stage of B cell development, and that this negative regulation might be required for normal B cell development.…”

Section: Discussionmentioning

confidence: 90%

“…Intriguingly, the transcription factor Spi-C (Prf), which is closely related to PU.1 and Spi-B, was initially cloned in a screen for factors which could occupy PU.1 DNA binding sites (17). Spi-C has extremely weak transcription-promoting activity, and unlike PU.1 and Spi-B, cannot interact with IRF-4 to synergistically activate gene expression on Ets/IRF composite elements (17,65). Spi-C has an extremely restricted pattern of expression: its transcription is initiated at the pre-B cell stage of B cell development, it is expressed in mature B cells, and its transcription is extinguished in plasma cells (16,17).…”

Section: Discussionmentioning

confidence: 99%

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Analysis of Gene Expression and Ig Transcription in PU.1/Spi-B-Deficient Progenitor B Cell Lines

Schweitzer

DeKoter

2004

The Journal of Immunology

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A number of presumptive target genes for the Ets-family transcription factor PU.1 have been identified in the B cell lineage. However, the precise function of PU.1 in B cells has not been studied because targeted null mutation of the PU.1 gene results in a block to lymphomyeloid development at an early developmental stage. In this study, we take advantage of recently developed PU.1−/−Spi-B−/− IL-7 and stromal cell-dependent progenitor B (pro-B) cell lines to analyze the function of PU.1 and Spi-B in B cell development. We show that contrary to previously published expectations, PU.1 and/or Spi-B are not required for Ig H chain (IgH) gene transcription in pro-B cells. In fact, PU.1−/−Spi-B−/− pro-B cells have increased levels of IgH transcription compared with wild-type pro-B cells. In addition, high levels of Igκ transcription are induced after IL-7 withdrawal of wild-type or PU.1−/−Spi-B−/− pro-B cells. In contrast, we found that Igλ transcription is reduced in PU.1−/−Spi-B−/− pro-B cells relative to wild-type pro-B cells after IL-7 withdrawal. These results suggest that Igλ, but not IgH or Igκ, transcription, is dependent on PU.1 and/or Spi-B. The PU.1−/−Spi-B−/− pro-B cells have other phenotypic changes relative to wild-type pro-B cells including increased proliferation, increased CD25 expression, decreased c-Kit expression, and decreased RAG-1 expression. Taken together, our observations suggest that reduction of PU.1 and/or Spi-B activity in pro-B cells promotes their differentiation to a stage intermediate between late pro-B cells and large pre-B cells.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Analysis of Gene Expression and Ig Transcription in PU.1/Spi-B-Deficient Progenitor B Cell Lines

Schweitzer

DeKoter

2004

The Journal of Immunology

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“…This pattern of expression partially overlaps the other members of the Spi family, PU.1 and Spi-B, which are expressed throughout B cell development (33)(34)(35). Gel mobility shift analysis shows that Spi-C can bind to PU.1-binding sites in the Ig locus (32). However, Spi-C cannot form a ternary complex with IFN regulatory factor (IRF)-4 on DNA (32).…”

mentioning

confidence: 87%

“…Although the DNA-binding domain of Spi-C shares 59% aa identity to the DNA-binding domain of PU.1, the transactivation domains are divergent (30,31). Spi-C is predicted to be a 28-kDa protein, which is smaller than the 31-kDa PU.1 protein (32). Northern blot analysis shows high levels of Spi-C in the spleen (30,31).…”

mentioning

confidence: 99%

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Spi-C Has Opposing Effects to PU.1 on Gene Expression in Progenitor B Cells

Schweitzer

Huang

Kamath

et al. 2006

The Journal of Immunology

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The Ets transcription factor Spi-C, expressed in B cells and macrophages, is closely related to PU.1 and has the ability to recognize the same DNA consensus sequence. However, the function of Spi-C has yet to be determined. The purpose of this study is to further examine Spi-C activity in B cell development. First, using retroviral vectors to infect PU.1−/− fetal liver progenitors, Spi-C was found to be inefficient at inducing cytokine-dependent proliferation and differentiation of progenitor B (pro-B) cells or macrophages relative to PU.1 or Spi-B. Next, Spi-C was ectopically expressed in fetal liver-derived, IL-7-dependent pro-B cell lines. Wild-type (WT) pro-B cells ectopically expressing Spi-C (WT-Spi-C) have several phenotypic characteristics of pre-B cells such as increased CD25 and decreased c-Kit surface expression. In addition, WT-Spi-C pro-B cells express increased levels of IgH sterile transcripts and reduced levels of expression and transcription of the FcγRIIb gene. Gel-shift analysis suggests that Spi-C, ectopically expressed in pro-B cells, can bind PU.1 consensus sites in the IgH intronic enhancer and FcγRIIb promoter. Transient transfection analysis demonstrated that PU.1 functions to repress the IgH intronic enhancer and activate the FcγRIIb promoter, while Spi-C opposes these activities. WT-Spi-C pro-B cells have reduced levels of dimethylation on lysine 9 of histone H3 within the IgH 3′ regulatory region, indicating that Spi-C can contribute to removal of repressive features in the IgH locus. Overall, these studies suggest that Spi-C may promote B cell differentiation by modulating the activity of PU.1-dependent genes.

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B‐1a cells are imprinted by the microenvironment in spleen and peritoneum

et al. 2007

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B‐1a cells are found mainly in the peritoneal cavity of mice but are also present in the spleen. Gene expression profiling defined many genes differentially expressed in B‐1a cells from these two sites. To see whether this gene expression pattern was imprinted by the particular microenvironment, peritoneal or spleen cells from recombinant L2 mice mainly consisting of B‐1a cells were adoptively transferred into Rag1–/– mice. Re‐isolated peritoneal and splenic B‐1a cells were analyzed for expression of three indicator genes – vcam‐1, adamdec1 and spi‐c. The expression of these genes was up‐regulated in splenic and down‐regulated in peritoneal cells. This particular pattern was observed for peritoneal or splenic donor cells transferred either intraperitoneally or intravenously. Similar results were obtained when levels of surface IgM or frequencies of Mac‐1+ B‐1 cells were compared after transfer. This suggests that the environment induces the particular genetic program of B‐1a cells and argues against an independent ontogeny.

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SPI-C, a PU-box binding ETS protein expressed temporarily during B-cell development and in macrophages, contains an acidic transactivation domain located to the N-terminus

Cited by 17 publications

References 31 publications

Analysis of Gene Expression and Ig Transcription in PU.1/Spi-B-Deficient Progenitor B Cell Lines

Analysis of Gene Expression and Ig Transcription in PU.1/Spi-B-Deficient Progenitor B Cell Lines

Spi-C Has Opposing Effects to PU.1 on Gene Expression in Progenitor B Cells

B‐1a cells are imprinted by the microenvironment in spleen and peritoneum

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