Octamer independent activation of transcription from the kappa immunoglobulin germline promoter

Prabhu, Anila; O'Brien, Darin P.; Weisner, Georgia L.; Fulton, Regan; Ness, Brian G. Van

doi:10.1093/nar/24.23.4805

Cited by 8 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The POU transcription factor Oct-1 is ubiquitously expressed (46) and is involved in the transcription regulation of numerous genes, among which are H2B (10), small nuclear RNAs (11,50), and Ig heavy chain and kappa light chain genes (12,36). Oct-1 can also repress von Willebrand factor (42), VCAM-1 (17,18), or interleukin-8 expression (57,58).…”

Section: Discussionmentioning

confidence: 99%

“…The ability of Oct-1 to regulate expression of proteins involved in cell cycle regulation (3,10,27), apoptosis (16,22), and immunity (5,12,17,18,33,34,36,58) and Oct-1 activation in response to stress signals (16,22,41,60), including viral infection (1), suggest an important role for Oct-1 in a defense mechanism against cellular stress. Accordingly, here we show that Oct-1-deficient MEFs exhibit increased endogenous IFN-A gene expression and modification in the pattern of IFN-A subtypes after virus induction.…”

Section: Vol 25 2005 Oct-1 Represses Ifn-a Gene Expression After Inmentioning

confidence: 99%

See 1 more Smart Citation

The POU Transcription Factor Oct-1 Represses Virus-Induced Interferon A Gene Expression

Mésplède¹,

Island²,

Christeff³

et al. 2005

Molecular and Cellular Biology

View full text Add to dashboard Cite

Alpha interferon (IFN-␣Alpha interferon (IFN-␣) and IFN-␤ are able to interfere with viral infection. They exert a vast array of biologic functions, including growth arrest, cell differentiation, and immune system regulation (for reviews, see references 28 and 51). This regulation extends from innate immunity to cellular and humoral adaptive immune responses. A strict control of expression is needed to prevent detrimental effects of unregulated IFN. IFN transcription is coordinately induced in human and mouse cells infected by virus. Multiple IFN-A subtypes exhibit differences in expression of their individual mRNAs.IFN-A transcription is regulated by a number of different activators and repressors. Among these factors, the interferon regulatory factors (IRFs) play an important role in the stimulation of cellular antiviral defense mechanisms in different cell types. IRFs regulate transcription by interacting with gene promoter sequences. Until now, repressors involved in negative regulation of the IFN-A genes have not been well characterized (for a review, see reference 29). We have shown that in addition to substitutions in proximal virus responsive element A (VRE-A) (2), the low expression levels of the IFN-A11 and IFN-A5 genes after virus induction are also due to the presence of a distal negative regulatory element (DNRE) of 20 bp, which is delimited upstream of VRE-A (20, 25, 26). The analysis of the DNRE responsible for the virus-induced transcription repression of some IFN-A promoters led us to study the homeodomain transcription factor Pitx1 (25). Upon virus induction, Pitx1 negatively regulates the transcription of DNREcontaining IFN-A11 and IFN-A5 promoters (20,25). We have recently shown that Pitx1 inhibits the IRF-3 and IRF-7 transcription activation of the IFN-A11 and IFN-A5 promoters and interacts physically with .Here we show that the POU protein Oct-1 binds in vitro to the DNRE and in vivo to the endogenous IFN-A11 promoter in mock-induced and induced cells. Furthermore, Oct-1 represses IFN-A11 expression upon IRF overexpression. Moreover, we show that Oct-1-deficient MEFs exhibit increased in vivo IFN-A gene expression and increased antiviral activity. Finally, the IFN-A expression pattern is modified in Oct-1-deficient MEFs. The broad representation of effective and potent octamer-like sequences within IFN-A promoters suggests an important role for Oct-1 in IFN-A regulation. We suggest this could have implications in IFN-␣-based combinatorial therapies. MATERIALS AND METHODSDNA transfection, viral induction, and transfection assays. Murine L929 cells were transfected by the standard calcium phosphate precipitation method as previously described (26). Newcastle disease virus (NDV) induction was carried out 24 h later. The mock-induced cells were set up as described above except that no NDV was added. Cells were harvested 24 h postinduction, and cytoplasm extracts were prepared. Luciferase activity was measured in cell lysates by using commercial reagents (Promega). Transfection efficiency was de...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Vol 25 2005 Oct-1 Represses Ifn-a Gene Expression After Inmentioning

confidence: 99%

The POU Transcription Factor Oct-1 Represses Virus-Induced Interferon A Gene Expression

Mésplède¹,

Island²,

Christeff³

et al. 2005

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…The most relevant members of the POU transcription factor family involved in the control of expression of the IgH genes are Oct2, which is predominantly expressed in B cells, and the more ubiquitous Oct1 (8,9). Oct2 and Oct1 seem to be essential for the promoter and enhancer function of IgH genes (10,11).…”

mentioning

confidence: 99%

“…Functionally, Oct2 activity is dependent on phosphorylation and alternative splicing (17)(18)(19)(20)(21), although it seems that the level of its expression can be used as a marker of B-cell lineage and differentiation (10,11,22,23). The activity of Oct1 can also be modified by phosphorylation (21).…”

mentioning

confidence: 99%

Analysis of Octamer-Binding Transcription Factors Oct2 and Oct1 and their coactivator BOB.1/OBF.1 in Lymphomas

et al. 2002

View full text Add to dashboard Cite

Oct1 and Oct2 are transcription factors of the POU homeo-domain family that bind to the Ig gene octamer sites, regulating B-cell-specific genes. The function of these transcription factors is dependent on the activity of B-cell-restricted coactivators such as BOB.1/OBF.1. Independent studies of the expression of these proteins in non-Hodgkin's lymphoma have been restricted to single markers, and most lack data concerning immunohistochemical expression. Thus, we have investigated the expression of Oct1, Oct2, and BOB.1/OBF.1 in human reactive lymphoid tissue and in a series of 140 Hodgkin and non-Hodgkin's lymphomas.None of these proteins was found to be restricted to B cells, although only B cells expressed high levels of all three markers. Additionally, germinal center B cells showed stronger Oct2 and BOB.1/OBF.1 staining. Consequently, most B-cell lymphomas showed reactivity for all three antibodies. Oct2 expression was significantly higher in germinal center-derived lymphomas, although other B-cell lymphomas also displayed a high level of Oct2 expression.Although T-cell lymphomas and Hodgkin's lymphomas expressed some of these proteins, they commonly exhibited less reactivity than B-cell lymphomas.Despite not being entirely cell-specific, the strong nuclear expression of Oct2 and BOB.1/OBF.1 by germinal centerderived lymphomas makes these antibodies a potentially useful tool in lymphoma diagnosis.

show abstract

“…Our focus in this paper has been on the kappa intron enhancer because of its importance in activation of kappa germ line transcription in pre-B cells (14,39). In addition, the inducible accessibility of the intron enhancer as measured by DNase I hypersensitivity (38) may represent some of the earliest events involved in providing accessibility of the locus to the V(D)J recombinase.…”

Section: Discussionmentioning

confidence: 99%

Coordinate Transcription and V(D)J Recombination of the Kappa Immunoglobulin Light-Chain Locus: NF-κB-Dependent and -Independent Pathways of Activation

O'Brien

Oltz

Ness

1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

To further elucidate the potential role of mitogens and cytokines in regulation of the kappa immunoglobulin light-chain locus, we have characterized the activation of transcription factor binding, kappa germ line transcription, DNase I hypersensitivity, and V -to-J recombination upon induction of model pre-B-cell lines. We find that both lipopolysaccharide (LPS) and gamma interferon (IFN-␥) are capable of activating germ line transcription, DNase I hypersensitivity, and recombination of the kappa locus. We also find that transforming growth factor ␤ is capable of completely inhibiting LPS activation of transcription and recombination but has no apparent effect on activation of transcription factor binding, It is becoming increasingly clear that the tissue-specific and developmentally regulated transcription and recombination of immunoglobulin (Ig) gene segments represent overlapping points of control during B-cell development. The concomitant activation of transcription and recombination of all Ig loci has led to the suggestion that transcription of unrearranged Ig genes plays a key role in regulating recombination (23, 31, 37, 44-46, 55, 60, 61). A number of observations have provided strong support for this hypothesis. First, while a common V(D)J recombinase is expressed in both B cells and T cells, functional recombination of Ig genes is restricted to B cells, where they are also transcriptionally active (62). While ectopic expression of the recombinase activating genes RAG-1 and RAG-2 has been shown to confer V(D)J recombinase activity to integrated and extrachromosomal substrates in nonlymphoid cells, the endogenous Ig loci, which are transcriptionally silent in these cells, do not undergo recombination (19,25,33). In addition, it has been demonstrated previously that induction of germ line transcription of the unrearranged kappa Ig lightchain and heavy-chain loci is accompanied by an increased frequency of gene rearrangement (44, 45). More direct evidence that cis-acting transcriptional regulatory elements are involved in recombination has been demonstrated by integration of recombination substrates by using transfection approaches (5, 6, 11, 24, 35), transgenic approaches (15-17, 20, 21), and targeted knockouts of endogenous sequences (18,48,54,59).While there is strong evidence that cis-acting transcriptional regulatory regions within the kappa Ig light-chain locus play a role in recombination, the mechanism by which they regulate recombination and the trans-acting factors involved have yet to be elucidated. The observation that cells are able to regulate the ability of the endogenous kappa locus to serve as a substrate for the V(D)J recombinase has led to the suggestion that transcription may target the locus by providing accessibility of the locus to the recombinase (see reviews in references 32, 39, and 47). The mechanism by which transcription may mediate accessibility is not clear; however, changes in local chromatin structure within the kappa locus have been shown to occur upon transcriptional ac...

show abstract

Octamer independent activation of transcription from the kappa immunoglobulin germline promoter

Cited by 8 publications

References 33 publications

The POU Transcription Factor Oct-1 Represses Virus-Induced Interferon A Gene Expression

The POU Transcription Factor Oct-1 Represses Virus-Induced Interferon A Gene Expression

Analysis of Octamer-Binding Transcription Factors Oct2 and Oct1 and their coactivator BOB.1/OBF.1 in Lymphomas

Coordinate Transcription and V(D)J Recombination of the Kappa Immunoglobulin Light-Chain Locus: NF-κB-Dependent and -Independent Pathways of Activation

Contact Info

Product

Resources

About