Computational promoter analysis of mouse, rat and human antimicrobial peptide-coding genes

Brahmachary, Manisha; Schönbach, Christian; Yang, Liang; Huang, Enli; Tan, Sin Lam; Chowdhary, Rajesh; Krishnan, S. P. T.; Lin, Chin-Yo; Hume, David; Cui, Kai; Kawai, Jun; Carninci, Piero; Hayashizaki, Yoshihide; Bajic, Vladimir B.

doi:10.1186/1471-2105-7-s5-s8

Cited by 26 publications

(13 citation statements)

References 63 publications

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“…Promoter analysis also revealed putative HNF1A and NF-kB TFBS in DEFB-VL. GR and NF-kB binding sites have previously been found in the promoters of defensins and suggest antimicrobial activity (Brahmachary et al 2006). Despite the similarity between DEFB-VL and the betadefensins, the spacing of cysteines within the DEFB-VL peptide differs slightly from the beta-defensins, and its amino acid sequence is more similar to that of the OvDLPs than it is to that of the beta-defensins (Supplemental Table 1).…”

Section: Features Of the Defensin And Ovdlp Genesmentioning

confidence: 89%

“…These promoters are also present in three of the defensins. All beta-defensins have predicted HNF1A binding sites, and beta-defensins 1-5 have predicted GATA4 binding sites, which suggest tissue specificity (Brahmachary et al 2006). DEFB-VL and beta-defensin 5 have predicted NF-kB binding sites, but only DEFB-VL possesses a glucocorticoid receptor (GR) transcription factor binding site (TFBS).…”

Section: Features Of the Defensin And Ovdlp Genesmentioning

confidence: 99%

“…Preliminary results were compared within the beta-defensin promoters and the betadefensin and OvDLP promoters. Preliminary results were also compared with known beta-defensin transcription factor binding sites (Brahmachary et al 2006). …”

Section: Promoter Analysis Of Ovdlps and Defensinsmentioning

confidence: 99%

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Defensins and the convergent evolution of platypus and reptile venom genes

Whittington¹,

Papenfuss²,

Bansal³

et al. 2008

Genome Res.

131

104

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When the platypus (Ornithorhynchus anatinus) was first discovered, it was thought to be a taxidermist's hoax, as it has a blend of mammalian and reptilian features. It is a most remarkable mammal, not only because it lays eggs but also because it is venomous. Rather than delivering venom through a bite, as do snakes and shrews, male platypuses have venomous spurs on each hind leg. The platypus genome sequence provides a unique opportunity to unravel the evolutionary history of many of these interesting features. While searching the platypus genome for the sequences of antimicrobial defensin genes, we identified three Ornithorhynchus venom defensin-like peptide (OvDLP) genes, which produce the major components of platypus venom. We show that gene duplication and subsequent functional diversification of beta-defensins gave rise to these platypus OvDLPs. The OvDLP genes are located adjacent to the beta-defensins and share similar gene organization and peptide structures. Intriguingly, some species of snakes and lizards also produce venoms containing similar molecules called crotamines and crotamine-like peptides. This led us to trace the evolutionary origins of other components of platypus and reptile venom. Here we show that several venom components have evolved separately in the platypus and reptiles. Convergent evolution has repeatedly selected genes coding for proteins containing specific structural motifs as templates for venom molecules.

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Section: Features Of the Defensin And Ovdlp Genesmentioning

confidence: 89%

Section: Features Of the Defensin And Ovdlp Genesmentioning

confidence: 99%

See 1 more Smart Citation

Defensins and the convergent evolution of platypus and reptile venom genes

Whittington¹,

Papenfuss²,

Bansal³

et al. 2008

Genome Res.

131

104

View full text Add to dashboard Cite

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“…49 These receptors also express various families of AmPs-20, 17 and 15 families, respectively, out of the 22 analyzed by Brahmachary. 50 As the concentration of 1,25-D accumulates within the nucleated cells, our model predicts that it would increasingly occupy the ligand-binding pockets of these receptors, displacing their endogenous ligands. For example, in the case of alpha-thyroid, the agonist T3 would have to compete with the antagonist 1,25-D for access to the receptor ligandbinding pockets.…”

Section: Communities Of Microbes Drive Autoimmune Diseasementioning

confidence: 89%

Immunostimulation in the era of the metagenome

Proal

Albert

Blaney³

et al. 2011

Cell Mol Immunol

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Microbes are increasingly being implicated in autoimmune disease. This calls for a re-evaluation of how these chronic inflammatory illnesses are routinely treated. The standard of care for autoimmune disease remains the use of medications that slow the immune response, while treatments aimed at eradicating microbes seek the exact opposite-stimulation of the innate immune response. Immunostimulation is complicated by a cascade of sequelae, including exacerbated inflammation, which occurs in response to microbial death. Over the past 8 years, we have collaborated with American and international clinical professionals to research a model-based treatment for inflammatory disease. This intervention, designed to stimulate the innate immune response, has required a reevaluation of disease progression and amelioration. Paramount is the inherent conflict between palliation and microbicidal efficacy. Increased microbicidal activity was experienced as immunopathology-a temporary worsening of symptoms. Further studies are needed, but they will require careful planning to manage this immunopathology.

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“…GC-rich housekeeping gene promoters are enriched in Sp1 binding motifs, which are also detected in the promoters and enhancers of genes expressed in hematopoietic and epithelial cells. Here, the Sp1 binding motif appears to cooperate with lineage-restricted factors in directing expression (22). CREB-H of the CREB/ATF family participates in liver-specific expression within the box-B element (23).…”

Section: Analysis Of Promoter Sequencesmentioning

confidence: 99%