The Human V-PreB Promoter Is a Target for Coordinated Activation by Early B Cell Factor and E47

Gisler, Ramiro; Sigvardsson, Mikael

doi:10.4049/jimmunol.168.10.5130

Cited by 35 publications

(27 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 and VpreB were activated in Ba/F3 pro-B cells by EBF and "forced dimers" of E47 (45), and recent studies suggest that these proteins activate mb-1 transcription in HeLa cells (M. Sigvardsson, unpublished observations). In addition to our studies of the mb-1 promoter, evidence was obtained for cooperative assembly of EBF:E47 ternary complexes on the 5 (37, 44) and VpreB (15) promoters. The molecular basis for these interactions is not understood, but synergism between the factors on the 5 promoter involves template-dependent assembly of complexes requiring their respective DNA-binding and dimerization domains (44).…”

Section: Discussionsupporting

confidence: 52%

Early B-Cell Factor, E2A, and Pax-5 Cooperate To Activate the Early B Cell-Specific mb-1 Promoter

Sigvardsson¹,

Clark

Fitzsimmons

et al. 2002

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

Previous studies have suggested that the early-B-cell-specific mb-1(Ig␣) promoter is regulated by EBF and Pax-5. Here, we used in vivo footprinting assays to detect occupation of binding sites in endogenous mb-1 promoters at various stages of B-cell differentiation. In addition to EBF and Pax-5 binding sites, we detected occupancy of a consensus binding site for E2A proteins (E box) in pre-B cells. EBF and E box sites are crucial for promoter function in transfected pre-B cells, and EBF and E2A proteins synergistically activated the promoter in transfected HeLa cells. Other data suggest that EBF and E box sites are less important for promoter function at later stages of differentiation, whereas binding sites for Pax-5 (and its Ets ternary complex partners) are required for promoter function in all mb-1-expressing cells. Using DNA microarrays, we found that expression of endogenous mb-1 transcripts correlates most closely with EBF expression and negatively with Id1, an inhibitor of E2A protein function, further linking regulation of the mb-1 gene with EBF and E2A. Together, our studies demonstrate the complexity of factors regulating tissue-specific transcription and support the concept that EBF, E2A, and Pax-5 cooperate to activate target genes in early B-cell development.

show abstract

Section: Discussionsupporting

confidence: 52%

Early B-Cell Factor, E2A, and Pax-5 Cooperate To Activate the Early B Cell-Specific mb-1 Promoter

Sigvardsson¹,

Clark

Fitzsimmons

et al. 2002

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…This is despite a reduction in the levels Rag1 expression and that of the surrogate light chain gene VpreB. VpreB has been shown to be a direct target of EBF in both mice and humans, [38][39][40] explaining why its expression is reduced in PU.1 ⌬/⌬CD19 mice.…”

Section: Discussionmentioning

confidence: 99%

The development of functional B lymphocytes in conditional PU.1 knock-out mice

Polli

Dakic

Light

et al. 2005

Blood

View full text Add to dashboard Cite

“…Two of them (5 0 À62 and 5 0 À97) map in the promoter region of the gene, but fall outside the known transcription factor-binding sites. 21 SNP (5 0 À97) is present in P14 together with the S122L amino-acid change that is predicted to have an impact on the protein structure. SNP (5 0 À62) is present in two patients (P1 and P18).…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia

et al. 2007

View full text Add to dashboard Cite

Autosomal-recessive agammaglobulinemia is a rare and heterogeneous disorder, characterized by early-onset infections, profound hypogammaglobulinemia of all immunoglobulin isotypes and absence of circulating B lymphocytes. To investigate the molecular basis of the disease, 23 patients with early-onset disease and no mutations in Bruton tyrosine kinase, the gene responsible for X-linked agammaglobulinemia, were selected and analyzed by direct sequencing of candidate genes. Two novel mutations in the m heavy chain (mHC) gene (IGHM) were identified in three patients belonging to two unrelated families. A fourth patient carries a previously described G4A nucleotide substitution at the À1 position of an alternative splice site in IGHM; here, we demonstrate that this mutation is indeed responsible for aberrant splicing. Comparison of bone marrow cytofluorimetric profiles in two patients carrying different mutations in the IGHM gene suggests a genotype-phenotype correlation with the stage at which B-cell development is blocked. Several new single nucleotide polymorphisms (SNPs) both in the mHC and in the l5-like/VpreB-coding genes were identified. Two unrelated patients carry compound heterozygous variations in the VpreB1 gene that may be involved in disease ethiology.

show abstract

The Human V-PreB Promoter Is a Target for Coordinated Activation by Early B Cell Factor and E47

Cited by 35 publications

References 52 publications

Early B-Cell Factor, E2A, and Pax-5 Cooperate To Activate the Early B Cell-Specific mb-1 Promoter

Early B-Cell Factor, E2A, and Pax-5 Cooperate To Activate the Early B Cell-Specific mb-1 Promoter

The development of functional B lymphocytes in conditional PU.1 knock-out mice

Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia

Contact Info

Product

Resources

About