Using altered specificity Oct-1 and Oct-2 mutants to analyze the regulation of immunoglobulin gene transcription

Shah, Pratik; Bertolino, Eric; Singh, Harinder

doi:10.1093/emboj/16.23.7105

Cited by 62 publications

(48 citation statements)

References 65 publications

(144 reference statements)

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“…Overexpression Experiments-The plasmids used included C/EBP␤, Oct-1 (wild type, mutated), and p65 (14,33,34). RcCMV (Invitrogen, Groningen, Netherlands) containing no insert was used as a negative control.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional Inhibition of Interleukin-8 Expression in Tumor Necrosis Factor-tolerant Cells

Weber

Sydlik

Quirling

et al. 2003

Journal of Biological Chemistry

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There is some evidence that the potent cytokine tumor necrosis factor (TNF) is able to induce tolerance after repeated stimulation of cells. To investigate the molecular mechanisms mediating this phenomenon, the expression of interleukin-8 (IL-8), which is regulated by transcription factors NF-B and C/EBP␤, was monitored under TNF tolerance conditions. Pretreatment of monocytic cells for 72 h with low TNF doses inhibited TNFinduced (restimulation with a high dose) IL-8 promoterdependent transcription as well as IL-8 production. Under these conditions neither activation of NF-B nor I B proteolysis was affected after TNF re-stimulation, albeit a slightly reduced I B-␣ level was found in the TNF pretreated but not re-stimulated sample. Remarkably, in tolerant cells an increased binding of C/EBP␤ to its IL-8 promoter-specific DNA motif as well as an elevated association of C/EBP␤ protein with p65-containing NF-B complexes was observed. Finally, overexpression of C/EBP␤, but not p65 or Oct-1, markedly prevented TNFinduced IL-8 promoter-dependent transcription. Taken together, these data indicate that the expression of IL-8 is inhibited at the transcriptional level in TNF-tolerant cells and C/EBP␤ is involved under these conditions in mediating the negative-regulatory effects, a mechanism that may play a role in inflammatory processes such as sepsis.

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Section: Methodsmentioning

confidence: 99%

Transcriptional Inhibition of Interleukin-8 Expression in Tumor Necrosis Factor-tolerant Cells

Weber

Sydlik

Quirling

et al. 2003

Journal of Biological Chemistry

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“…Transfection studies have demonstrated that OCT.1 can compensate the absence of OCT.2. 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.…”

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

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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.

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“…Plasmid Constructions-The Oct-1 expression vector pcDNA3HA Oct-1 was a gift from Dr. H. Singh (30). The in vitro transcription and translation vector for Oct-1 p6His Oct-1 and OCA-B expression vector pRc OCA-B were from Dr. R. G. Roeder (11,31).…”

Section: Methodsmentioning

confidence: 99%

Silencing Mediator for Retinoid and Thyroid Hormone Receptors Interacts with Octamer Transcription Factor-1 and Acts as a Transcriptional Repressor

Kakizawa

Miyamoto

Ichikawa

et al. 2001

Journal of Biological Chemistry

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Octamer transcription factor-1 (Oct-1) is a member of the POU (Pit-1, Oct-1, unc-86) family of transcription factors and is involved in the transcriptional regulation of a variety of gene expressions related to cell cycle regulation, development, and hormonal signals. It has been shown that Oct-1 acts not only as a transcriptional activator but also as a transcriptional repressor for certain genes. The mechanism of the repressive function of Oct-1 has not been well understood. Here we demonstrate by using the glutathione S-transferase pull-down assays and coimmunoprecipitation assays that the POU domain of Oct-1 directly interacts with a silencing mediator for retinoid and thyroid hormone receptors (SMRT). The interaction surfaces are located in the Cterminal region of SMRT, which are different from previously described silencing domains I and II or receptor interacting domains I and II. In transient transfection assays in COS1 cells, overexpression of SMRT attenuated the augmentation of Oct-1 transcriptional activity by OBF-1/OCA-B, activator for Oct-1. In pull-down assays, increasing amounts of SMRT could compete the binding of OCA-B to Oct-1 POU domain. The activity of Oct-1 could be determined by a regulated balance between SMRT and OCA-B. Furthermore, cotransfected unliganded thyroid hormone receptor enhanced the transactivation by Oct-1, and addition of 3,3,5-tri-iodo-L-thyronine obliterated the stimulatory effects. Consequently, in the presence of cotransfected thyroid hormone receptor, the octamer response element acts as an element negatively regulated by 3,3,5-tri-iodo-L-thyronine. The results suggest that the transcriptional activity of Oct-1 can be modulated by interaction through its POU domain by a silencing mediator SMRT resulting in the cross-talk between Oct-1 and nuclear receptors.Octamer transcription factor-1 (Oct-1) 1 activates the octamer motif containing gene promoters that are ubiquitously as well as tissue-specifically expressed genes such as histone H2B, the small nuclear RNA, and Ig (1-3). Oct-1 is a member of a family of transcription factors characterized by the presence of a bipartite DNA-binding domain (POU domain). The POU domain consists of two conserved regions, a POU-specific domain and a POU homeodomain (4, 5). The both subdomains have a helixturn-helix motif, acting not only as a DNA-binding domain but also as a protein-protein interaction domain. A number of transcription factors have been identified to interact with the POU domains of Oct-1 such as TBP, TFIIB, HMG2, and Oct-binding factor 1 (OBF-1) also referred to as Oct-1-associated coactivator (OCA-B) (6 -11). It has been shown that Oct-1 interacts with nuclear hormone receptors such as retinoid X receptor, thyroid hormone receptor (TR), and glucocorticoid receptor and influences their transcriptional activity (12-14). Oct-1 possesses not only transactivation function but also repression function; von Willebrand factor promoter (15), prolactin gene promoter (16), or rGH promoter (14) was shown to be down-regulated by Oct...

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Using altered specificity Oct-1 and Oct-2 mutants to analyze the regulation of immunoglobulin gene transcription

Cited by 62 publications

References 65 publications

Transcriptional Inhibition of Interleukin-8 Expression in Tumor Necrosis Factor-tolerant Cells

Transcriptional Inhibition of Interleukin-8 Expression in Tumor Necrosis Factor-tolerant Cells

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

Silencing Mediator for Retinoid and Thyroid Hormone Receptors Interacts with Octamer Transcription Factor-1 and Acts as a Transcriptional Repressor

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