OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins

Strubin, Michel; Newell, John W.; Matthias, Patrick

doi:10.1016/0092-8674(95)90500-6

Cited by 367 publications

(361 citation statements)

References 53 publications

Supporting

Mentioning

338

Contrasting

Unclassified

Order By: Relevance

“…The fact that the function of Oct-3/4 depends on the cellular environment also suggests that the key to understanding how the Oct-3/4 protein activates or represses transcription of cellular genes will also rely on the identification of additional cell-restricted activities, such as the B-cell-specific coactivator OCA-B/OBF-1/BOB1, which can specifically activate tran- scription through interactions with either Oct-1 or Oct-2 (13,64), or the OTX-related homeobox transcription factor that interacts with Pit-1 (67). It is possible that Oct-3/4 can switch between an activator and a repressor due to its interactions with auxiliary adapter proteins which Oct-3/4 recruits to the Rex-1 promoter.…”

Section: Discussionmentioning

confidence: 99%

Rex-1, a Gene Encoding a Transcription Factor Expressed in the Early Embryo, Is Regulated via Oct-3/4 and Oct-6 Binding to an Octamer Site and a Novel Protein, Rox-1, Binding to an Adjacent Site

Ben-Shushan

Thompson

Gudas

et al. 1998

Molecular and Cellular Biology

225

167

View full text Add to dashboard Cite

The Rex-1 (Zfp-42) gene, which encodes an acidic zinc finger protein, is expressed at high levels in embryonic stem (ES) and F9 teratocarcinoma cells. Prior analysis identified an octamer motif in the Rex-1 promoter which is required for promoter activity in undifferentiated F9 cells and is involved in retinoic acid (RA)-associated reduction in expression. We show here that the Oct-3/4 transcription factor, but not Oct-1, can either activate or repress the Rex-1 promoter, depending on the cellular environment. Rex-1 repression is enhanced by E1A. The protein domain required for Oct-3/4 activation was mapped to amino acids 1 to 35, whereas the domain required for Oct-3/4 repression was mapped to amino acids 61 to 126, suggesting that the molecular mechanisms underlying transcriptional activation and repression differ. Like Oct-3/4, Oct-6 can also lower the expression of the Rex-1 promoter via the octamer site, and the amino-terminal portion of Oct-6 mediates this repression. In addition to the octamer motif, a novel positive regulatory element, located immediately 5 of the octamer motif, was identified in the Rex-1 promoter. Mutations in this element greatly reduce Rex-1 promoter activity in F9 cells. High levels of a binding protein(s), designated Rox-1, recognize this novel DNA element in F9 cells, and this binding activity is reduced following RA treatment. Taken together, these results indicate that the Rex-1 promoter is regulated by specific octamer family members in early embryonic cells and that a novel element also contributes to Rex-1 expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Rex-1, a Gene Encoding a Transcription Factor Expressed in the Early Embryo, Is Regulated via Oct-3/4 and Oct-6 Binding to an Octamer Site and a Novel Protein, Rox-1, Binding to an Adjacent Site

Ben-Shushan

Thompson

Gudas

et al. 1998

Molecular and Cellular Biology

225

167

View full text Add to dashboard Cite

show abstract

“…This interaction is required for the activation of viral immediate-early genes containing a TAATGARAT motif in an Oct-1-dependent manner. Second, the lymphoid-specific factor Bob-1/OBF-1/OCA-B specifically binds to the POU domains of Oct-1 and Oct-2 but not to other octamer-binding proteins (11,23,24,43) and mediates the transactivation of immunoglobulin gene templates by Oct-1 or Oct-2. In addition to these specific interactions, a more promiscuous type of interaction exists between POU domains and high-mobility-group (HMG) proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Several POU factors require cellular coactivators for full activity. For example, a B-cell-specific cofactor (11,23,24,43) interacts with the POU domains of Oct-1 and Oct-2, whereas a Schwann cell-specific coactivator has been postulated to interact with the transactivation domain of SCIP/Tst-1/Oct-6 (8,28,54). By analogy, the Oct-4 transactivation domains could also require a specific cofactor in P19 cells.…”

Section: Oct-4 Contains Two Separate Transactivation Domainsmentioning

confidence: 99%

The Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain

Brehm

Ohbo

Schöler

1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

The POU transcription factor Oct-4 is expressed in totipotent and pluripotent cells of the early mouse embryo and the germ cell lineage. Transactivation capacities of regions flanking the DNA binding domain of Oct-4 were analyzed in undifferentiated and differentiated cell lines. The amino-and carboxy-terminal regions (N domain and C domain) fused to the Gal4 DNA binding domain both functioned as transactivation domains in all cell lines tested. However, the C domain failed to activate transcription in some cell lines in the context of the native protein. The underlying regulatory mechanism appears to involve the POU domain of Oct-4 and can discriminate between different POU domains, since constructs in which the C domain was instead fused to the POU domain of Pit-1 were again equally active in all cell lines. These results indicate that the C domain is subject to cell-type-specific regulation mediated by the Oct-4 POU domain. Phosphopeptide analysis revealed that the cell-type-specific difference of C-domain activity correlates with a difference in Oct-4 phosphorylation status. Since Oct-4 is expressed in a variety of distinct cell types during murine embryogenesis, these results suggest an additional regulatory mechanism for determining Oct-4 function in rapidly changing cell types during development.The octamer motif is a regulatory DNA element involved in both ubiquitous and cell-type-specific gene expression and is recognized by a family of eukaryotic transcription factors that share a homologous bipartite DNA binding domain, the POU domain (13,44,52,55). The POU domain consists of two structurally independent subdomains: a 75-amino-acid aminoterminal region specific for this class of transcription factors (POU S ) and a 60-amino-acid carboxy-terminal homeodomain (POU H ). Both subdomains make specific contacts with DNA through a helix-turn-helix structure (17) and are connected by a variable linker that can vary from 15 to 56 amino acids (aa) in length.Regions outside the POU domain are not critical for DNA binding and show little sequence conservation. In many cases,

show abstract

“…21 Octamer functions are dependent on the presence of the B-cell-restricted coactivator BOB.1, which is a transcription factor necessary for B-cell development, inducing the formation of germinal centres. 16,22,23 With the aim of evaluating the expression of transcription factors at the protein level in HRS cells in the largest series of cases reported until now, we performed an immunohistochemical study for OCT.1, OCT.2 and BOB.1 in 325 cases of classical Hodgkin's lymphoma, correlating the results with the expression of the B-cell markers CD20, CD79a, B-cell-specific activator protein (BSAP) and MUM.1, the presence of Epstein-Barr virus and the histological subtype. For this purpose, we used the recently developed tissue microarray technology that allows the simultaneous analysis of a large number of cases and whose feasibility in Hodgkin's lymphoma analysis has been demonstrated.…”

mentioning

confidence: 99%

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

et al. 2004

View full text Add to dashboard Cite

Hodgkin's lymphoma can be considered in most cases a B-cell lymphoma due to the presence of potentially functional immunoglobulin (Ig) gene rearrangements in the neoplastic cells. In contrast to lymphocytepredominant Hodgkin's lymphoma, Hodgkin/Reed-Sternberg (HRS) cells from classical Hodgkin's lymphoma have low frequency of B-cell marker expression and lack Ig light and Ig heavy messenger RNA. Recent studies have shown transcription machinery deficiency in Hodgkin's lymphoma caused by an absence of the transcription factors OCT.1, OCT.2 and/or BOB.1. By using the tissue microarray technique, we have performed an immunohistochemical study of OCT.1, OCT.2 and BOB.1 in 325 classical Hodgkin's lymphoma cases. The results have been correlated with the expression of the B-cell markers CD20, CD79a, B-cell-specific activator protein (BSAP) and MUM.1, the presence of Epstein-Barr virus and the histological subtype. The percentage of CD20 and CD79a positivity was low (18 and 18%, respectively), whereas MUM.1 and BSAP were positive in the majority of cases. Considering the positive cases with independence of the intensity of staining, 62% of them expressed OCT.2, 59% OCT.1 and 37% BOB.1. Nevertheless, when we considered only the strongly positive cases, the results were similar to those previously described by others. No statistical association was found between the transcription factor expression, histological subtype and Epstein-Barr virus presence. To our knowledge, this is the largest series of classical Hodgkin's lymphoma cases in which the expression of transcription factors has been studied. We have found a notorious percentage of cases displaying weak positivity for OCT.2 and BOB.1 factors in HRS cells. We propose that other mechanisms different from the absence of transcription factors OCT.2 and BOB.1 might be involved in the control of Ig transcription and B lineage in classical Hodgkin's lymphoma.

show abstract

OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins

Cited by 367 publications

References 53 publications

Rex-1, a Gene Encoding a Transcription Factor Expressed in the Early Embryo, Is Regulated via Oct-3/4 and Oct-6 Binding to an Octamer Site and a Novel Protein, Rox-1, Binding to an Adjacent Site

Rex-1, a Gene Encoding a Transcription Factor Expressed in the Early Embryo, Is Regulated via Oct-3/4 and Oct-6 Binding to an Octamer Site and a Novel Protein, Rox-1, Binding to an Adjacent Site

The Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

Contact Info

Product

Resources

About