Regulation of immunoglobulin gene transcription by labile represser factor(s)

Kitamura, Daisuke; Maeda, Hiroaki; Araki, Kazuo; Kudo, Akira; Watanabe, Takeshi

doi:10.1002/eji.1830170906

Cited by 16 publications

(8 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The emerging mechanism which accounts for the specificity of the IgH enhancer in vivo is that both cellspecific and ubiquitous positively acting transcription factors interact with and account for the activity of the enhancer in B cells. The inactivity of the enhancer in non-B cells results both from the absence of some of positive transcription factors which can functionally interact with the enhancer, and from the presence of negative elements which influence its cell-type specificity (6)(7)31,40).…”

Section: Discussionmentioning

confidence: 99%

Mutational analysis of the contribution of sequence motifs within the IgH enhancer to tissue specific transcriptional activation

Pérez-Mutul¹,

Macchi²,

Wasylyk³

1988

Nucleic Acids Research

View full text Add to dashboard Cite

We have investigated the role of sequence motifs in the immunoglobulin heavy chain (IgH) enhancer on its activity in myeloma and fibroblast cell-lines. In transient transfection assays the transcription stimulatory activity of the enhancer is decreased in myeloma cells by mutating the E motifs 1, 2 and 3, the core motifs C1, C2, C3 and the octamer motif (OC) and in fibroblasts by mutating E2, E3, and C2. Our results suggest that transcription factors binding to E1, C1, C3 and OC contribute in a positive manner to the tissue specificity of the IgH enhancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Mutational analysis of the contribution of sequence motifs within the IgH enhancer to tissue specific transcriptional activation

Pérez-Mutul¹,

Macchi²,

Wasylyk³

1988

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Among these, the octamer sequence ATT1lGCAT has been shown to be a B-cellspecific motif that binds both ubiquitous (octl) and B-cellspecific (oct2A and oct2B) factors (10,22,35,36,38). On the other hand, negative transcriptional control has also been suggested by several groups (17,21). Two repressor elements, one located 5' of the E2 motif and the other found 3' of the E4 and octamer motifs, have been identified by deletion analysis (2,16,18,32,33,41,43).…”

mentioning

confidence: 99%

Positive and negative regulation of immunoglobulin gene expression by a novel B-cell-specific enhancer element.

1991

View full text Add to dashboard Cite

A new B-cell-specific enhancer element has been identified 3' of E4 and the octamerlike motifs in the human immunoglobulin heavy-chain gene enhancer. Tandem copies of this 67-bp Mnll-AluI fragment, when fused to the chloramphenicol acetyltransferase gene driven by the conalbumin promoter, stimulated transcription in B cells but not in Jurkat T cells or HeLa cells. Footprinting analysis revealed that the identical sequence CCGAAACTGAAAAGG, designated E6, was protected by nuclear extracts from B cells, T cells, or HeLa cels.Gel mobility shift assays using a synthetic E6 motif detected a B-cell-specific complex in addition to a ubiquitous band found also in T ceUls and HeLa cells. In agreement with the results of gel retardation assays, tandem copies of the E6 motif stimulated transcription in ARH77 and Raji cells but not in Jurkat or HeLa cells. Furthermore, a mutant E6 motif lost both in vitro binding activity and in vivo enhancer activity. In striking contrast to the mouse Ig heavy-chain enhancer, in which the octamer motif acts as a B-cell-specific enhancer element, the human enhancer contains an octamerlike sequence with one base substitution which bound octamer-binding proteins with only very low affinity and showed no enhancer activity of its own. Interestingly, the Mnll-AluI fragment could suppress the basal-level activity of the conalbumin promoter in both Jurkat and HeLa cells. Moreover, simian virus 40 enhancer activity was blocked by the MnII-AluI fragment in HeLa cells but not in B cells. Thus, the novel enhancer element identified in this study is probably a target site for both positive and negative factors.Transcription of immunoglobulin (Ig) genes is regulated by at least two elements: promoters 5' of V regions and an enhancer within the J (joining)-C (constant) intron (3,7,11,13,25,27,28,31). The J-C intron enhancer probably not only is involved in the regulation of transcription of rearranged Ig genes but also plays a crucial role in the regulation of Ig gene rearrangement during B-cell differentiation (8). The activity of the Ig gene enhancer is strictly regulated by multiple trans-acting factors that interact with each other and with cis-acting enhancer elements. Thus, identification and characterization of such factors, especially B-cell-specific ones, is important for elucidating the mechanism by which B cells differentiate from bone marrow stem cells.The mouse Ig heavy-chain gene enhancer has been investigated by many groups. Several enhancer motifs such as El to E5 and the octamer have been identified (6). These motifs bind trans-acting factors that act collectively to enhance transcription (15,23,34,40). Among these, the octamer sequence ATT1lGCAT has been shown to be a B-cellspecific motif that binds both ubiquitous (octl) and B-cellspecific (oct2A and oct2B) factors (10,22,35,36,38). On the other hand, negative transcriptional control has also been suggested by several groups (17, 21). Two repressor elements, one located 5' of the E2 motif and the other found 3' of the E4 and octamer mo...

show abstract

“…Reports have appeared of a tissue-specific enhancer (4, 27, [30][31][32], a tissue-specific promoter (10,12,13,26,32), tissue-specific silencer elements (17,18,20,43,45), and perhaps sequences residing in the body of the gene (14).…”

mentioning

confidence: 99%

New B-lymphocyte-specific enhancer-binding protein.

Dorn¹,

Benoist²,

Mathis³

1989

Mol. Cell. Biol.

View full text Add to dashboard Cite

We report the discovery of a new B-lymphocyte-specific enhancer-binding protein. A series of gel retardation assays using fragments that scan the -2172 to -1180 region of the major histocompatibility complex class II gene E. reveal a site (W) that serves as the recognition sequence for two nuclear proteins, one B-cell restricted and the other ubiquitously occurring. Certain characteristics of the NF-W1 and NF-W2 pair recall the OTF-2/ NF-A2 and OTF-1/NF-Al pair that binds to the immunoglobulin octamer, but we demonstrate that the two protein pairs are distinguishable by several criteria. NF-W1 and NF-W2 interact differentially with their common GTTGCATC binding site, display a different affinity for it, and have molecular weights that differ by about 20,000. Yet, proteolysis experiments and cross-linking analyses indicate that the two W complexes show structural relatedness.

show abstract

Regulation of immunoglobulin gene transcription by labile represser factor(s)

Cited by 16 publications

References 69 publications

Mutational analysis of the contribution of sequence motifs within the IgH enhancer to tissue specific transcriptional activation

Mutational analysis of the contribution of sequence motifs within the IgH enhancer to tissue specific transcriptional activation

Positive and negative regulation of immunoglobulin gene expression by a novel B-cell-specific enhancer element.

New B-lymphocyte-specific enhancer-binding protein.

Contact Info

Product

Resources

About