A human early B-cell factor-like protein participates in the regulation of the human CD19 promoter

Gisler, Ramiro; Åkerblad, Peter; Sigvardsson, Mikael

doi:10.1016/s0161-5890(99)00092-9

Cited by 21 publications

(18 citation statements)

References 42 publications

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“…EBF is expressed early in B cell development and is required for execution of the B cell programme. EBF binds to functionally important promoter sites of several B cell specific genes such as CD19, CD79a (mb-1) and the surrogate light chain gene 14.1 (Gisler et al, 1999(Gisler et al, , 2000. RNase protection mapping demonstrated very low but significant levels of EBF transcripts in all the cell lines except for HD-MyZ that was devoid of EBF transcripts ( Figure 2c).…”

Section: Resultsmentioning

confidence: 99%

“…The human CD19 promoter is a target for both EBF and BSAP (Nutt et al, 1998;Gisler et al, 1999). In KM-H2 cells, EBF on its own resulted in a threefold increase in promoter activity, BSAP on its own in some fivefold increase, and when both factors were coexpressed, promoter activity was elevated some fivefold ( Figure 6e).…”

Section: Expression Of B Cell Transcription Factors Pu1 and Pax-5 Ismentioning

confidence: 98%

“…The reporter plasmids pKappaLucE (wild-type murine k promoter) and pKappa0 -LucE (mutated octamer site) are described in Strubin et al (1995). The 14.1 and mb-1 promoter-controlled luciferase reporters are described in Gisler et al (2000) and the CD19 promoter-controlled reporter in Gisler et al (1999). 3*PU.1-Luc is from Nerlov and Graf (1998).…”

Section: Transfection and Reporter Gene Assaysmentioning

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: Expression Of B Cell Transcription Factors Pu1 and Pax-5 Ismentioning

confidence: 98%

Section: Transfection and Reporter Gene Assaysmentioning

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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“…Notably, CD19 is regulated by EBF in the human (Gisler et al, 1999). While it has not been shown to be under direct EBF control in the mouse, it is likely that EBF promotes mouse CD19 expression in B-cells, through regulation of Pax-5/BSAP signaling.…”

Section: Discussionmentioning

confidence: 99%

Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B-cell leukemia

et al. 2004

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Retroviral insertions that activate proto-oncogenes are a primary cause of tumors in certain strains of mice. The AKXD recombinant inbred mice are predisposed to a variety of leukemias and lymphomas as a result of viral integration. One common insertion site, the ecotropic viral insertion site 3 (Evi3), has been implicated in most B-cell tumors in the AKXD-27 strain. The Evi3 gene encodes a zinc-finger protein with sequence similarity to the Early B-cell Factor-Associated Zinc-finger gene (EBFAZ). We show that the Evi3 gene is overexpressed in several tumors with viral insertions at Evi3, which results in the upregulation of Early B-cell Factor (EBF)-target gene expression, suggesting that Evi3 modulates EBF activity. Reconstitution of primary leukemia cells showed that these tumors express high densities of the Bcell surface proteins CD19 and CD38, which are EBF targets. Using a transactivation assay, we show that the terminal six zinc-fingers of Evi3 are required for modification of EBF activity. This is the first evidence that Evi3 expression in tumors alters the level of EBF target genes, and the first characterization of the Evi3 protein domains required for modulation of EBF activity. Further, these data imply that Evi3 misexpression initiates tumorigenesis by perturbing B-cell development via an interaction with EBF.

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“…Previous reports demonstrated that activation of murine and human promoters of Cd19 genes, which encode a costimulatory receptor on B cells, is dependent on EBF and Pax5 (24)(25)(26). Therefore, we measured Cd19 transcripts in M.2 cells expressing EBF:ER, Pax5:ER, or both factors in the presence of Brg1/Brm-or Mi-2␤-specific shRNAs and 4-OHT (Fig.…”

Section: -Oht-dependent Ebf and Pax5mentioning

confidence: 99%

Opposing effects of SWI/SNF and Mi-2/NuRD chromatin remodeling complexes on epigenetic reprogramming by EBF and Pax5

Gao

Lukin

Ramírez

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

128

132

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Transcriptionally silent genes are maintained in inaccessible chromatin. Accessibility of these genes requires their modification by chromatin remodeling complexes (CRCs), which are recruited to promoters by sequence-specific DNA-binding proteins. Early B-cell factor (EBF), which is crucial for B-cell lineage specification, reprograms mb-1 (Ig-␣) promoters by increasing chromatin accessibility and initiating the loss of DNA methylation. In turn, this facilitates promoter activation by Pax5. Here, we investigated the roles of ATP-dependent CRCs in these mechanisms. Fusion of EBF and Pax5 with the ligand-binding domain of ER␣ allowed for 4-hydroxytamoxifen-dependent, synergistic activation of mb-1 transcription in plasmacytoma cells. Knockdown of the SWI/SNF ATPases Brg1 and Brm inhibited transcriptional activation by EBF:ER and Pax5:ER. In contrast, knock-down of the Mi-2/NuRD complex subunit Mi-2␤ greatly enhanced chromatin accessibility and mb-1 transcription in response to the activators. The reduction of Mi-2␤ also propagated DNA demethylation in response to EBF:ER and Pax5:ER, resulting in fully unmethylated mb-1 promoters. In EBF-or EBF/Pax5-deficient fetal liver cells, both EBF and Pax5 were required for efficient demethylation of mb-1 promoters. Together, our data suggest that Mi-2/NuRD is important for the maintenance of hypermethylated chromatin in B cells. We conclude that SWI/SNF and Mi-2/NuRD function in opposition to enable or limit the reprogramming of genes by EBF and Pax5 during B-cell development.DNA methylation ͉ mb-1 promoter ͉ Cd19 promoter ͉ chromatin accessibility T he development of B cells from progenitor cells in the bone marrow is controlled by a network of transcriptional regulators (reviewed in 1). Early B-cell Factor (EBF; also known as EBF1/O/E-1/COE1) plays an integral role in this network and has been implicated as a major determinant of the B-cell fate (2, 3). In the absence of EBF, B-cell development is arrested at an early progenitor stage (3, 4). EBF is essential for the rearrangement and expression of Ig (Ig) genes in B cells and is required for expression of the B-cell commitment factor Pax5. EBF and Pax5 synergistically activate transcription of B cell-specific genes including mb-1 (Cd79a), which encodes the Ig-␣ subunit of the pre-B and B-cell receptors (5). We have proposed that EBF functions as a 'pioneer' factor by controlling the epigenetic states of its target genes (6). In response to EBF, the accessibility of mb-1 promoter chromatin is increased, while DNA methylation of the promoter is decreased.Specific biochemical interactions necessary for the pioneer functions of EBF have not been identified. However, transitions between active and inactive states of chromatin can be mediated by the recruitment of chromatin-remodeling complexes (CRCs) by transcription factors (7). CRCs serve as 'molecular motors' that mediate changes in the relative positions of nucleosomes. In this regard, CRCs of the mammalian SWI/SNF (related to yeast switch/sucrose non-Fermenter) subfamily ...

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A human early B-cell factor-like protein participates in the regulation of the human CD19 promoter

Cited by 21 publications

References 42 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

Evi3, a zinc-finger protein related to EBFAZ, regulates EBF activity in B-cell leukemia

Opposing effects of SWI/SNF and Mi-2/NuRD chromatin remodeling complexes on epigenetic reprogramming by EBF and Pax5

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