Functional analysis of the human annexin I and VI gene promoters

Donnelly, Shaun R.; Moss, Stephen E.

doi:10.1042/bj3320681

Cited by 26 publications

(23 citation statements)

References 31 publications

(9 reference statements)

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“…Alternatively, Maderna et al 30 had proposed that an increased expression of Anx A1, another bridging protein in the phagocytic synapse, might contribute to the Dex-dependent enhancement of apoptotic cell removal. In our cell system, consistent with previous reports, 31,32 we did not observe a Dex-dependent induction of Anx A1 expression. Hence, this is unlikely to be causative for the phagocytosispromoting effect examined in the present study.…”

Section: Discussionsupporting

confidence: 82%

Milk fat globule-EGF factor 8 mediates the enhancement of apoptotic cell clearance by glucocorticoids

et al. 2013

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The phagocytic clearance of apoptotic cells is essential to prevent chronic inflammation and autoimmunity. The phosphatidylserine-binding protein milk fat globule-EGF factor 8 (MFG-E8) is a major opsonin for apoptotic cells, and MFG-E8 À / À mice spontaneously develop a lupus-like disease. Similar to human systemic lupus erythematosus (SLE), the murine disease is associated with an impaired clearance of apoptotic cells. SLE is routinely treated with glucocorticoids (GCs), whose anti-inflammatory effects are consentaneously attributed to the transrepression of pro-inflammatory cytokines. Here, we show that the GC-mediated transactivation of MFG-E8 expression and the concomitantly enhanced elimination of apoptotic cells constitute a novel aspect in this context. Patients with chronic inflammation receiving high-dose prednisone therapy displayed substantially increased MFG-E8 mRNA levels in circulating monocytes. MFG-E8 induction was dependent on the GC receptor and several GC response elements within the MFG-E8 promoter. Most intriguingly, the inhibition of MFG-E8 induction by RNA interference or genetic knockout strongly reduced or completely abolished the phagocytosis-enhancing effect of GCs in vitro and in vivo. Thus, MFG-E8-dependent promotion of apoptotic cell clearance is a novel anti-inflammatory facet of GC treatment and renders MFG-E8 a prospective target for future therapeutic interventions in SLE.

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Section: Discussionsupporting

confidence: 82%

Milk fat globule-EGF factor 8 mediates the enhancement of apoptotic cell clearance by glucocorticoids

et al. 2013

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“…This nucleotide change does not change the amino acid sequence of the protein (Leu) (5). The TATA box and the CAAT box are the major regulatory elements needed for transcription of the gene (15,22); both are included in the screened promoter segment. Genotyping of identified variants.…”

Section: Methodsmentioning

confidence: 99%

“…A total of 41 subjects with type 2 diabetes from 26 families who presented excess allele sharing at chromosome 9 in the initial linkage study were chosen for the mutation screening of ANXA1. In these subjects and in two nondiabetic control subjects without family history of diabetes, the minimal promoter (22), the exons, and flanking intronic sequences were screened for mutations using the SSCP technique (23). All gels were scored manually by two independent readers, and all samples with a band pattern deviating from the expected band pattern (given from the two control subjects) were sequenced to find the causative variant.…”

Section: Methodsmentioning

confidence: 99%

“…No difference in either allele or genotype frequency was detected between the two groups (P ϭ 0.30 and P ϭ 0.84, respectively) ( Table 3). The (CA) [15][16][17][18][19][20][21][22][23][24][25] repeat was genotyped in the 440 subjects of the initial linkage study, but no improvement of the original NPL score was observed in this analysis (data not shown). ANXA1 is a good candidate gene for type 2 diabetes, considering its putative physiological role and location in a region on chromosome 9q21 to which we have detected suggestive linkage to type 2 diabetes.…”

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confidence: 99%

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Characterization of the Annexin I Gene and Evaluation of Its Role in Type 2 Diabetes

et al. 2001

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In a previous study, we identified suggestive linkage between type 2 diabetes and a locus on chromosome 9p13-q21. This region contains the gene annexin I (ANXA1), encoding a protein suggested to be involved in both insulin secretion and insulin action. In this study, we sequenced the exon/intron boundaries of the human ANXA1 gene and performed mutation screening in 41 individuals from the initial linkage study. We identified five single nucleotide polymorphisms A58G, A401G, intronic variance sequence (IVS)8-28A/G, IVS11 ؉31A/G, and IVS12-11T/G, which were further tested for association to diabetes in 197 parent/offspring trios using the transmission disequilibrium test. No significant association with type 2 diabetes was observed, although the common A allele of the ؉58A/G variant gave a 22:12 transmission distortion (P ‫؍‬ 0.12). This variant was further genotyped in 481 case and control subjects, but no difference in allele, genotype, or haplotype frequencies were observed between the groups. Further, a novel polymorphic (CA) 15-25 repeat in intron 11 was genotyped in the subjects included in the initial linkage study. No improvement of the original finding was observed. We therefore concluded that the ANXA1 gene is unlikely to harbor variants that contribute to risk of type 2 diabetes.

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“…Regulatory regions have been partially characterized in only three other annexin genes, i.e. annexin A1 in pigeon [22] and human [23][24][25][26] and those for human annexins A6 [26,27] and A7 [28]. Annexins A5 and A6 shared their most recent common ancestor 500-700 million years ago [20], yet they retain no apparent homology in noncoding regions.…”

Section: Introductionmentioning

confidence: 99%

Functional analysis of the human annexin A5 gene promoter: a downstream DNA element and an upstream long terminal repeat regulate transcription

Carcedo

Iglesias

Bances

et al. 2001

Biochemical Journal

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Human annexin A5 is a ubiquitous protein implicated in diverse signal transduction processes associated with cell growth and differentiation, and its gene regulation is an important component of this function. Promoter transcriptional activity was determined for a wide 5′ portion of the human annexin A5 gene, from bp −1275 to +79 relative to the most 5′ of several discrete transcription start points. Transfection experiments carried out in HeLa cells identified the segment from bp −202 to +79 as the minimal promoter conferring optimal transcriptional activity. Two canonical Sp1 sites in the immediate 5′ flanking region of a CpG island were required for significant transcription. Strong repressive activity in the distal promoter region between bp −717 to −1153 was attributed to the presence of an endogenous retroviral long terminal repeat, homologous with long terminal repeat 47B. The downstream sequence from bp position +31 to +79 in untranslated exon 1 was also essential for transcription, as its deletion from any of the plasmid constructs abolished activity in transfection assays. Electrophoretic mobility-shift assays, Southwestern-blot analysis and affinity chromatography were used to identify a protein doublet of relative molecular mass 35kDa that bound an octanucleotide palindromic sequence in exon 1. The DNA cis-element resembled an E-box, but did not bind higher molecular mass transcription factors, such as upstream stimulatory factor or activator protein 4. The discovery of a downstream element crucial for annexin A5 gene transcription, and its interaction with a potentially novel transcription factor or complex, may provide a clue to understanding the initiation of transcription by TATA-less, multiple start site promoters.

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Functional analysis of the human annexin I and VI gene promoters

Cited by 26 publications

References 31 publications

Milk fat globule-EGF factor 8 mediates the enhancement of apoptotic cell clearance by glucocorticoids

Milk fat globule-EGF factor 8 mediates the enhancement of apoptotic cell clearance by glucocorticoids

Characterization of the Annexin I Gene and Evaluation of Its Role in Type 2 Diabetes

Functional analysis of the human annexin A5 gene promoter: a downstream DNA element and an upstream long terminal repeat regulate transcription

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