Spi-C, a Novel Ets Protein That Is Temporally Regulated during B Lymphocyte Development

Bemark, Mats; Mårtensson, Annica; Liberg, David; Leanderson, Tomas

doi:10.1074/jbc.274.15.10259

Cited by 47 publications

(59 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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). 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).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Schweitzer

DeKoter

2004

The Journal of Immunology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Spi-C (also called Prf) shares 40% overall sequence identity with PU.1, and shares 59% identity in the DNA binding domain (16,17). PU.1 and Spi-B function as strong transcriptional activators, while Spi-C has weak transcription activation ability (17).…”

Section: Cells (4)mentioning

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

View full text Add to dashboard Cite

show abstract

“…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).…”

mentioning

confidence: 99%

“…Spi-C/Prf (PU.1-related factor) was identified simultaneously in two independent laboratories through a yeast-one hybrid method using the PU.1-binding sites of the Ig 3Ј enhancer and SP6 promoter sequences as bait (30,31). 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).…”

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

“…Spic is a member of the ets gene family and its gene product has been described as having opposing effects to PU.1 during B-cell maturation. 60,61 Spic has also been implicated, with STAT-6, in regulating germline IgE transcription. 62 Mef2c (myocyte enhancer factor 2C) has previously been defined as a transcription factor found in B cells following inflammatory stimuli.…”

Section: Discussionmentioning

confidence: 99%

Defining a transcriptional fingerprint of murine splenic B-cell development

et al. 2008

View full text Add to dashboard Cite

B-cell development occurs in a stepwise fashion that can be followed by the expression of B cell-specific surface markers. In this study, we wished to identify proteins that could contribute to the changes in expression of such markers. By using RNA from freshly isolated B220 þ cells, we hoped to reduce the effect of artifacts that occur during the isolation and amplification steps necessary to use flow cytometry analysis-sorted subsets in microarray experiments. Analyses comparing expression patterns from B220 þ 2-week bone marrow (pro-B, pre-B, immature B cells), 2-week spleen (predominantly transitional cells) and 8-week spleen (mainly mature B cells) yielded hundreds of genes. We also examined the B cell-activating factor (BAFF)-dependent effects on immature splenic B cells by comparing expression patterns in the spleen between 2-week A/J vs 2-week A/WySnJ mice, which lack functional BAFF receptor signaling. Genes that showed the expression differences between spleen and bone marrow samples were then analyzed through quantitative PCR on B-cell subsets isolated using two different sorting protocols. A comparison of the results from our study with the results from other analyses showed not only some overlap of preferentially expressed genes but also an expansion of other genes potentially involved in B-cell development.

show abstract

Spi-C, a Novel Ets Protein That Is Temporally Regulated during B Lymphocyte Development

Cited by 47 publications

References 46 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

Defining a transcriptional fingerprint of murine splenic B-cell development

Contact Info

Product

Resources

About