A Functional Composite Cis-Element for NFκB and RBPJκ in the Rat Pregnancy-Specific Glycoprotein Gene1

Wang, Chorng-Der; Chang, Geen-Dong; Lee, Yung-Kang; Chen, Hung−Wen

doi:10.1095/biolreprod65.5.1437

Cited by 9 publications

(5 citation statements)

References 40 publications

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“…We also detected CSL bound to both promoters; however, treatment with GSI showed no effect on CSL binding. The CSL binding site overlaps with that of the transcription factor NF- κ B (18–20). Previously, we reported that N1ICD also can interact with NF- κ B to directly regulate IFN- γ (17).…”

Section: Resultsmentioning

confidence: 99%

Notch Regulates Cytolytic Effector Function in CD8+ T Cells

Cho¹,

Shin

Miele

et al. 2009

The Journal of Immunology

136

139

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The maturation of naive CD8+ T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8+ effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.

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Section: Resultsmentioning

confidence: 99%

Notch Regulates Cytolytic Effector Function in CD8+ T Cells

Cho¹,

Shin

Miele

et al. 2009

The Journal of Immunology

136

139

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“…We performed sequence analysis with different transcription factor binding site software programs to identify possible trans elements that may bind this second functional retroviral segment of the EDNRB LTR between positions 168 and 247, which we have called LPE2. Using this approach, three candidate binding sites were identified for which transcription factors had been previously found to be involved in placental expression; the heterodimer E47/Thing1 (8), Oct-1 (5, 25), and NF-B (24). These motifs present within LPE2 will be referred to as A, B, and C, as the identities of the proteins that bound to FIG.…”

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confidence: 99%

Functional Analysis of the Endogenous Retroviral Promoter of the Human Endothelin B Receptor Gene

Landry

Mager

2003

J Virol

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We previously reported that the long terminal repeats (LTRs) of retroviral elements belonging to the HERV-E family contribute to the expression of the human apolipoprotein C1 (APOC1) and endothelin B receptor (EDNRB) genes by providing alternative promoters. While both LTRs were shown to promote transcription in vivo and in vitro, their respective activity and tissue specificity appeared to differ even though they shared a high degree of sequence identity. In the present study, we further characterized the promoter of the EDNRB LTR and delineated the regions and motifs required for strong activity. We confirmed the placenta-restricted expression of the LTR by transient transfections and quantitative real-time PCR and determined that the retroviral promoter contributes significantly to the level of EDNRB transcripts in placenta, where chimeric mRNAs were found to represent 15% of overall EDNRB mRNAs. Transient transfection of 5 deletion constructs in cells of placental origin identified a motif, named LPE1, between positions 111 and 122 of the EDNRB LTR necessary for transcriptional activity. Removal of this region, which contains a putative SP1 binding site, abolished promoter activity. A second enhancing region resides between positions 175 and 215 of the LTR and was termed LPE2. Interestingly, this section contained three binding sites that were not present in the APOC1 LTR due to minor nucleotide differences. The predicted motifs in the EDNRB LTR were found to likely act in symbiosis as modifications to any of the three sites reduced transcription by one-third while alterations to all three eliminated promoter activity. The results from this study illustrate how slight variations in transcriptional regulatory sequences can have a profound effect on promoter activity and demonstrate the complex regulatory effects of human endogenous retrovirus elements on human gene expression.

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“…In this regard, we have shown recently that deletion of TGFβ-activated Kinase-1 (TAK1) and subsequent impairment of NF-κB activation is accompanied with high expression of the transcription factor RBPJ, which acts as a transcriptional repressor of osteoclastogenesis 28 . Earlier studies have shown that the NF-κB member p65/RelA, an immediate downstream target of NEMO/IKK2 classical pathway, and RBPJ share an overlapping binding site at different gene promoters, including NFATc1 33 34 . In other studies, our group and Zhao et al .…”

Section: Discussionmentioning

confidence: 99%

Myeloid Deletion of Nemo Causes Osteopetrosis in Mice Owing to Upregulation of Transcriptional Repressors

Swarnkar

Shim

Nasir

et al. 2016

Sci Rep

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The transcription factor NF-κB is central to numerous physiologic processes including bone development, and its activation is controlled by IKKγ (also called NEMO), the regulatory subunit of IKK complex. NEMO is X-linked, and mutations in this gene result in Incontinentia Pigmenti in human hemizygous females. In mice, global deficiency causes embryonic lethality. In addition, certain point mutations in the NEMO (IKBKG) human gene manifest skeletal defects implicating NEMO in the regulation of bone homeostasis. To specifically investigate such role, we conditionally deleted Nemo from osteoclast and myeloid progenitors. Morphometric, histologic, and molecular analyses demonstrate that myeloid NEMO deletion causes osteopetrosis in mice. Mechanistically, NEMO deficiency hampered activation of IKK complex in osteoclast precursors, causing arrest of osteoclastogenesis and apoptosis. Interestingly, inhibiting apoptosis by genetic ablation of TNFr1 significantly increased cell survival, but failed to rescue osteoclastogenesis or reverse osteopetrosis. Based on this observation, we analyzed the expression of different regulators of osteoclastogenesis and discovered that NEMO deletion leads to increased RBPJ expression, resulting in a decrease of Blimp1 expression. Consequently, expression of IRF8 and Bcl6 which are targets of Blimp1 and potent osteoclastogenic transcriptional repressors, is increased. Thus, NEMO governs survival and osteoclast differentiation programs through serial regulation of multiple transcription factors.

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A Functional Composite Cis-Element for NFκB and RBPJκ in the Rat Pregnancy-Specific Glycoprotein Gene1

Cited by 9 publications

References 40 publications

Notch Regulates Cytolytic Effector Function in CD8+ T Cells

Notch Regulates Cytolytic Effector Function in CD8+ T Cells

Functional Analysis of the Endogenous Retroviral Promoter of the Human Endothelin B Receptor Gene

Myeloid Deletion of Nemo Causes Osteopetrosis in Mice Owing to Upregulation of Transcriptional Repressors

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