Early B cell factor binds to a site critical for λ5 core enhancer activity

Mårtensson, Annica; Mårtensson, Inga‐Lill

doi:10.1002/eji.1830270145

Cited by 26 publications

(46 citation statements)

References 32 publications

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“…The exact explanation for the B-cell phenotype observed in EBF-1-deficient mice is still unclear even though the protein has been suggested to be directly involved in the transcription regulation of several genes encoding components of the pre-Band B-cell receptor. These include the surrogate light-chain genes (41,50,53,57,58) and the B-cell receptor signal transducing molecules B29 (2), mb-1 (27,29) and Blk (3). The ability of EBF-1 to activate promoters controlling expression of the surrogate light chains appears to be conserved also in humans even though the primary DNA sequence of the promoters appears poorly preserved (24,25).…”

Section: O/e Proteins and B-lymphocyte Developmentmentioning

confidence: 99%

The EBF/Olf/Collier Family of Transcription Factors: Regulators of Differentiation in Cells Originating from All Three Embryonal Germ Layers

Liberg

Sigvardsson

Åkerblad

2002

Molecular and Cellular Biology

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One major mechanism for achieving cell-type-specific functions in somatic cells is the differential usage of stage-and tissue-specific genes. This is in large part regulated by transcription factors that interact directly with DNA elements controlling transcription of these genes. Several groups of transcription factors with key roles in cellular differentiation and function have been characterized, and the list of transactivating proteins with crucial functions in vivo is continuously growing. One group of evolutionarily conserved proteins with defined roles in a large variety of species are the basic helixloop-helix (bHLH) proteins (42,44). These factors are involved in a large number of differentiation processes, including such diverse events as sex determination in Drosophila melanogaster and B-lymphopoiesis in mice (9,15,38,42,48). In 1993, two independent reports presented a novel type of HLH protein with a dimerization domain containing two helices with homology to the second helix of the classical bHLH protein dimerization domain, but with a different type of DNA binding domain (DBD). This factor was cloned both in a Saccharomyces cerevisiae one-hybrid experiment designed to identify factors interacting with the olfactory-restricted olfactory marker protein-1 (OMP-1) promoter (69), and by biochemical purification of a factor interacting with the B-lymphocyte-restricted mb-1 promoter (27). It was accordingly named Olf-1, or early B-cell factor (EBF), which in turn led to the designation of the factor as O/E-1. Later reports showed that mice expressed at least three more members of this family, EBF2 (mMot1/O/E-3), EBF3 (O/E-2) (23, 40, 71), and O/E-4 (70), with a high degree of similarity in the DNA-binding and dimerization domains. Isolation of the O/E homologue Collier from D. melanogaster (12) provided a proof of principle for the existence of a new family of evolutionarily conserved proteins, and family members have now been cloned in several species (7,17,24,27,46,52,69) (Table 1). The biological roles of this protein family are beginning to be unraveled, and here we are compiling some of the available information about the roles of Collier/Olf/EBF (COE) proteins to give an overview of the known functions of this protein family in specific model systems and in different model species. BIOCHEMICAL FEATURES AND GENE ORGANIZATION OF COE PROTEINSThe COE protein family contains several conserved regions and the homology in the DBD between the evolutionarily most distally related proteins still remains above 80%. This is a strong indication that the specific structure is of crucial importance for the function of the protein and that the COE proteins are presenting a novel and unique DBD. COE factors bind DNA through a cysteine-and histidine-rich domain of about 250 amino acids located in the amino-terminal part of the proteins (Fig. 1A). Binding of EBF-1 requires Zn 2ϩ and, even though no sequence homology to known Zn finger domains can be found, three of the cysteines together with one of the histidine res...

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Section: O/e Proteins and B-lymphocyte Developmentmentioning

confidence: 99%

The EBF/Olf/Collier Family of Transcription Factors: Regulators of Differentiation in Cells Originating from All Three Embryonal Germ Layers

Liberg

Sigvardsson

Åkerblad

2002

Molecular and Cellular Biology

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“…Its gene product, together with VpreB1/VpreB2 and Ig heavy chain, forms the pre-B cell receptor (pre-BCR), which is crucial for normal B lymphocyte development and proliferation at the pre-B cell stage [2]. Expression of the murine Q 5 gene is regulated at the level of transcription, which is partly controlled by a region, 5' Q 5 , located immediately upstream of the coding sequence [3][4][5]. Detailed analyses in transient transfection assays have shown that the 722-bp 5' Q 5 fragment contains a promoter and an enhancer.…”

Section: Introductionmentioning

confidence: 99%

“…Detailed analyses in transient transfection assays have shown that the 722-bp 5' Q 5 fragment contains a promoter and an enhancer. The promoter, A Q 5 , is active in all cell types, whereas the enhancer, B Q 5 , is active only in pre-B cells [3,5]. An˚100-bp enhancer core, b Q 5 , that carries approximately 50% of the activity of the full-length enhancer has also been defined [5], but its cell type preference has not been determined.…”

Section: Introductionmentioning

confidence: 99%

“…The promoter, A Q 5 , is active in all cell types, whereas the enhancer, B Q 5 , is active only in pre-B cells [3,5]. An˚100-bp enhancer core, b Q 5 , that carries approximately 50% of the activity of the full-length enhancer has also been defined [5], but its cell type preference has not been determined. The importance of 5' Q 5 for expression and specificity has been further demonstrated in transgenic mice where a reporter gene was expressed in the expected lineageand stage-specific manner [6].…”

Section: Introductionmentioning

confidence: 99%

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PEBP2 and c-myb sites crucial for λ5 core enhancer activity in pre-B cells

et al. 2001

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“…One exemption is the promoter of the pre-B-cellspecific 5 gene (26,27), where E47 acts in synergy with EBF to stimulate transcription (58). This control element mediates stage-and lineage-specific expression of reporter genes both in transient transfections (32,33) and in transgenic mice (34). This makes the 5 promoter a useful model system to investigate B-cell-specific gene activation by bHLH proteins.…”

mentioning

confidence: 99%

Overlapping Expression of Early B-Cell Factor and Basic Helix-Loop-Helix Proteins as a Mechanism To Dictate B-Lineage-Specific Activity of the λ5 Promoter

Sigvardsson

2000

Molecular and Cellular Biology

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The basic helix-loop-helix (bHLH) transcription factors are a large group of proteins suggested to control key events in the development of B lymphocytes as well as of other cellular lineages. To examine how bHLH proteins activate a B-lineage-specific promoter, I investigated the ability of E47, E12, Heb, E2-2, and MyoD to activate the 5 surrogate light chain promoter. Comparison of the functional capacity of the E2A-encoded E47 and E12 proteins indicated that even though both were able to activate the 5 promoter and act in synergy with early B-cell factor (EBF), E47 displayed a higher functional activity than E12. An ability to act in synergy with EBF was also observed for Heb, E2-2, and MyoD, suggesting that these factors were functionally redundant in this regard. Mapping of functional domains in EBF and E47 revealed that the dimerization and DNA binding domains mediated the synergistic activity. Electrophoretic mobility shift assay analysis using the 5 part of the 5 promoter revealed formation of template-dependent heteromeric complexes between EBF and E47, suggesting that the synergistic mechanism involves cooperative binding to DNA. These findings propose a unique molecular function for E47 and provide overlapping expression with EBF as a molecular mechanism to direct B-cell-specific target gene activation by bHLH proteins.

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Early B cell factor binds to a site critical for λ5 core enhancer activity

Cited by 26 publications

References 32 publications

The EBF/Olf/Collier Family of Transcription Factors: Regulators of Differentiation in Cells Originating from All Three Embryonal Germ Layers

The EBF/Olf/Collier Family of Transcription Factors: Regulators of Differentiation in Cells Originating from All Three Embryonal Germ Layers

PEBP2 and c-myb sites crucial for λ5 core enhancer activity in pre-B cells

Overlapping Expression of Early B-Cell Factor and Basic Helix-Loop-Helix Proteins as a Mechanism To Dictate B-Lineage-Specific Activity of the λ5 Promoter

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