CREB / ATF proteins enhance the basal and CD154- and IL-4-induced transcriptional activity of the human Iγ1 proximal promoter

Bhushan, Ameesha; Covey, Lori R.

doi:10.1002/1521-4141(200102)31:2<653::aid-immu653>3.0.co;2-d

Cited by 10 publications

(13 citation statements)

References 44 publications

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“…However, the finding that mutations in the B6 site had a profound effect on transcription was both novel and unexpected. This putative NF-B site lies within a previously defined 36-bp element, shown to be functionally divergent between the I␥1 and I␥3 promoters, and is directly adjacent to multiple CREB/ATF binding sites implicated in optimal I␥1 promoter activity (31). Analysis of the different binding sites with respect to CD40L and IL-4 stimulation was conducted by transfecting the mutant B promoter constructs into Ramos B cells and culturing them with and without 293/CD40L cells in the presence and absence of IL-4 (Fig.…”

Section: Two Distinct Regions Are Important For Regulating I␥1 Transcmentioning

confidence: 91%

“…Transfection and stimulation of Ramos 2G6 cells (5 ϫ 10 6 per condition) were conducted exactly as described previously (31). After 48-h incubation at 37°C, cells were lysed and assayed for luciferase activity using the Dual-Luciferase assay kit (Promega).…”

Section: Transient Transfections and Coculture Conditionsmentioning

confidence: 92%

“…Specifically, we identified a 36-bp region in the I␥1 promoter that contained overlapping CREB and ATF-1/ATF-2 binding sites as well as a consensus NF-B site (B6) downstream and adjacent to the CREB site. High basal and IL-4/CD40L-induced responses corresponded to the binding of CREB/ATF proteins to motifs found in the I␥1 but not the I␥3 36-bp element (31).…”

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confidence: 99%

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A Novel NF-κB-Regulated Site within the Human Iγ1 Promoter Requires p300 for Optimal Transcriptional Activity

Dryer

Covey

2005

The Journal of Immunology

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Transcriptional activation of germline (GL) promoters occurs through binding of NF-κB to three evolutionarily conserved sites within a CD40 response region in the human and mouse GL Iγ and Iε promoters. Here we identify and characterize a novel NF-κB binding site (κB6) within the human GL Iγ1 promoter that plays an essential role in basal- and CD40-induced transcription. This site is adjacent to identified CREB/activating transcription factor (ATF) sites, present in the Iγ1 but not the Iγ3 promoter, which are important for the amplification of transcription. Our data suggest a cohesive protein complex regulating Iγ1 promoter activity because disruption of any individual NF-κB or CREB/ATF site markedly lowers the overall inducible activity of the promoter. In addition, alteration of helical phasing within the promoter indicates spatial orientation of CREB/ATF and NF-κB, proteins contributes directly to promoter activity. We found that CREB and p50 transactivators, as well as coactivator p300, interact in vivo with the Iγ1 promoter in the presence and absence of CD40 signaling in Ramos and primary B cells. However, the level of CREB and p300 binding differs as a consequence of activation in primary B cells. Furthermore, overexpression of p300, and not a mutant lacking acetyltransferase activity, significantly increases Iγ1 construct-specific transcription. Together these data support a model whereby CREB and multiple NF-κB complexes bind to the Iγ1 promoter and recruit p300. CD40 signals induce p300-dependent changes that result in optimal Iγ1 promoter activity.

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Section: Two Distinct Regions Are Important For Regulating I␥1 Transcmentioning

confidence: 91%

Section: Transient Transfections and Coculture Conditionsmentioning

confidence: 92%

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confidence: 99%

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A Novel NF-κB-Regulated Site within the Human Iγ1 Promoter Requires p300 for Optimal Transcriptional Activity

Dryer

Covey

2005

The Journal of Immunology

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“…Alternatively, CREB-1 may regulate expression of distinct Ab isotypes. This is consistent with the CREB binding sites in several Ig promoters, including IgA and IgG1 (44,59,60).…”

Section: Discussionmentioning

confidence: 99%

“…CREB/AP-1 family of proteins has been shown to regulate the expression of Ig gene (44). To test whether overexpression of dominant-negative CREB-1 in the mice alters the serum Ig, ELISA analysis of sera from 8-wk-old naive NTg and Tg mice was performed.…”

Section: Defective Humoral Immune Responses In Mcreb-1 Tg Micementioning

confidence: 99%

Differential Role for Cyclic AMP Response Element Binding Protein-1 in Multiple Stages of B Cell Development, Differentiation, and Survival

Chen¹,

Byrd

Muthusamy

2006

The Journal of Immunology

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CREB-1 is expressed in the bone marrow and in developing B cells. To determine the role of CREB-1 in developing B cells in the bone marrow, several lines of transgenic (Tg) mice overexpressing a dominant-negative Ser119-ala phosphomutant CREB-1 in the bone marrow were generated. Analysis of RNA and protein revealed expression of the transgene in the bone marrow. Flow cytometric analysis of bone marrow cells from Tg mice revealed ∼70% increase in pre-B1 (CD43+B220+CD24+(int)) and ∼60% decreased pre-BII (CD43+B220+CD24++(high)) cells, indicating a developmental block in pre-BI to pre-BII transition. Consistent with this, the Tg mice showed ∼4-fold decrease in immature and mature B cells in the bone marrow. RT-PCR analysis of RNA from Tg mice revealed increased JunB and c-Jun in pre-BII cells associated with decreased S-phase entry. Adoptive transfer of bone marrow cells into RAG-2−/− mice resulted in reconstitution of non-Tg but not Tg bone marrow-derived CD43+B220+CD24high population that is normally absent in RAG-2−/− mice. In the periphery, the Tg mice exhibited decreased CD21dimCD23highIgM+ follicular B cells in the spleen and increased B1a and B1b B cells in the peritoneum. While exhibiting normal Ab responses to T-independent Ags and primary response to the T-dependent Ag DNP-keyhole limpet hemocyanin, the Tg mice exhibited severely impaired secondary Ab responses. These studies provide the first evidence for a differential role for CRE-binding proteins in multiple stages of B cell development, functional maturation, and B1 and B2 B cells.

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IL-4-induced AID expression and its relevance to IgA class switch recombination

Kim

Park

et al. 2007

Biochemical and Biophysical Research Communications

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CREB / ATF proteins enhance the basal and CD154- and IL-4-induced transcriptional activity of the human Iγ1 proximal promoter

Cited by 10 publications

References 44 publications

A Novel NF-κB-Regulated Site within the Human Iγ1 Promoter Requires p300 for Optimal Transcriptional Activity

A Novel NF-κB-Regulated Site within the Human Iγ1 Promoter Requires p300 for Optimal Transcriptional Activity

Differential Role for Cyclic AMP Response Element Binding Protein-1 in Multiple Stages of B Cell Development, Differentiation, and Survival

IL-4-induced AID expression and its relevance to IgA class switch recombination

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