Species-specific Regulation of Toll-like Receptor 3 Genes in Men and Mice

The human apoptosis channel TRPM2 is stimulated by intracellular ADR-ribose and calcium. Recent studies show pronounced species-specific activation mechanisms. Our aim was to analyse the functional effect of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), commonly referred to as PIP2, on different TRPM2 orthologues. Moreover, we wished to identify the interaction site between TRPM2 and PIP2. We demonstrate a crucial role of PIP2, in the activation of TRPM2 orthologues of man, zebrafish, and sea anemone. Utilizing inside-out patch clamp recordings of HEK-293 cells transfected with TRPM2, differential effects of PIP2 that were dependent on the species variant became apparent. While depletion of PIP2 via polylysine uniformly caused complete inactivation of TRPM2, restoration of channel activity by artificial PIP2 differed widely. Human TRPM2 was the least sensitive species variant, making it the most susceptible one for regulation by changes in intramembranous PIP2 content. Furthermore, mutations of highly conserved positively charged amino acid residues in the membrane interfacial cavity reduced the PIP2 sensitivity in all three TRPM2 orthologues to varying degrees. We conclude that the membrane interfacial cavity acts as a uniform PIP2 binding site of TRPM2, facilitating channel activation in the presence of ADPR and Ca2+ in a species-specific manner.

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Combined Analysis of MicroRNome and 3′-UTRome Reveals a Species-specific Regulation of Progesterone Receptor Expression in the Endometrium of Rhesus Monkey

Journal of Biological Chemistry ◽

10.1074/jbc.m111.301275 ◽

2012 ◽

Vol 287 (17) ◽

pp. 13899-13910 ◽

Cited By ~ 24

Author(s):

Ji-Long Liu ◽

Xiao-Huan Liang ◽

Ren-Wei Su ◽

Wei Lei ◽

Bo Jia ◽

...

Keyword(s):

Progesterone Receptor ◽

Rhesus Monkey ◽

Receptor Expression ◽

Progesterone Receptor Expression ◽

Combined Analysis ◽

Specific Regulation ◽

Species Specific

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Chromatin remodeling in bovine embryos indicates species-specific regulation of genome activation

Nature Communications ◽

10.1038/s41467-020-18508-3 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Michelle M. Halstead ◽

Xin Ma ◽

Chuan Zhou ◽

Richard M. Schultz ◽

Pablo J. Ross

Keyword(s):

Preimplantation Development ◽

Open Chromatin ◽

Bovine Embryos ◽

Embryonic Genome ◽

Epigenetic Remodeling ◽

Profile Changes ◽

Specific Regulation ◽

Species Specific ◽

Genome Activation ◽

Cross Species Comparison

Abstract The shift from maternal to embryonic control is a critical developmental milestone in preimplantation development. Widespread transcriptomic and epigenetic remodeling facilitate this transition from terminally differentiated gametes to totipotent blastomeres, but the identity of transcription factors (TF) and genomic elements regulating embryonic genome activation (EGA) are poorly defined. The timing of EGA is species-specific, e.g., the timing of murine and human EGA differ significantly. To deepen our understanding of mammalian EGA, here we profile changes in open chromatin during bovine preimplantation development. Before EGA, open chromatin is enriched for maternal TF binding, similar to that observed in humans and mice. During EGA, homeobox factor binding becomes more prevalent and requires embryonic transcription. A cross-species comparison of open chromatin during preimplantation development reveals strong similarity in the regulatory circuitry underlying bovine and human EGA compared to mouse. Moreover, TFs associated with murine EGA are not enriched in cattle or humans, indicating that cattle may be a more informative model for human preimplantation development than mice.

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Species-specific regulation of fibrinogen synthesis with implications for porcine hepatocyte xenotransplantation

Xenotransplantation ◽

10.1111/xen.12110 ◽

2014 ◽

Vol 21 (5) ◽

pp. 444-453 ◽

Cited By ~ 8

Author(s):

Wolf Ramackers ◽

Johannes Klose ◽

Florian W. R. Vondran ◽

Harald Schrem ◽

Alexander Kaltenborn ◽

...

Keyword(s):

Porcine Hepatocyte ◽

Specific Regulation ◽

Species Specific

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Differential Activation of Human and Mouse Toll-Like Receptor 4 by the Adjuvant Candidate LpxL1 of Neisseria meningitidis

Infection and Immunity ◽

10.1128/iai.00005-08 ◽

2008 ◽

Vol 76 (8) ◽

pp. 3801-3807 ◽

Cited By ~ 56

Author(s):

Liana Steeghs ◽

A. Marijke Keestra ◽

Andries van Mourik ◽

Heli Uronen-Hansson ◽

Peter van der Ley ◽

...

Keyword(s):

Neisseria Meningitidis ◽

Lipid A ◽

Vaccine Development ◽

Meningococcal Vaccine ◽

Toll Like Receptor ◽

Wild Type ◽

Toll Like Receptor 4 ◽

Species Specific ◽

Human And Mouse ◽

Dc Maturation

ABSTRACT Neisseria meningitidis LpxL1 lipopolysaccharide (LPS) bearing penta-acylated lipid A is considered a promising adjuvant candidate for inclusion in future N. meningitidis vaccines, as it elicits a markedly reduced endotoxic response in human macrophages relative to that in wild-type (hexa-acylated) LPS, while it is an equally effective adjuvant in mice. As dendritic cells (DC) and Toll-like receptors (TLR) are regarded as central mediators in the initiation of an immune response, here we evaluated the ability of LpxL1 LPS to mature and to activate human DC and examined its TLR4-/MD-2-activating properties. Unexpectedly, purified LpxL1 LPS displayed minimal human DC-stimulating properties compared to wild-type LPS. Although whole bacteria induced DC maturation and activation irrespective of their type of LPS, the LpxL1 mutant failed to activate the human recombinant TLR4/MD-2 complex expressed in HeLa cells. Similarly, purified LpxL1 LPS was unable to activate human TLR4/MD-2 and it even acted as an antagonist of wild-type LPS. Both wild-type and LpxL1 LPSs activated the murine TLR4/MD-2 complex, consistent with their abilities to induce maturation and activation of murine DC. Assays with cells transfected with different combinations of human and murine TLR4 and MD-2 indicated that TLR4 was a more-major determinant of the LPS response than MD-2. The species-specific activation of the TLR4/MD-2 complex by LpxL1 LPS may have an impact on the use of LpxL1 LPS as an adjuvant and the use of murine immunization models in human meningococcal vaccine development.

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Transcriptional Regulation of Divergent Capsule Biosynthesis and Transport Operon Promoters in Serogroup BNeisseria meningitidis

Infection and Immunity ◽

10.1128/iai.69.4.2502-2511.2001 ◽

2001 ◽

Vol 69 (4) ◽

pp. 2502-2511 ◽

Cited By ~ 18

Author(s):

Yih-Ling Tzeng ◽

John S. Swartley ◽

Yoon K. Miller ◽

Rachel E. Nisbet ◽

Li-Jun Liu ◽

...

Keyword(s):

Transcriptional Regulation ◽

Sialic Acid ◽

Stationary Phase ◽

Intergenic Region ◽

Direct Repeat ◽

Intergenic Sequence ◽

Transcriptional Level ◽

Phase Growth ◽

Specific Regulation ◽

Species Specific

ABSTRACT The clinically important serogroups B, C, Y, and W-135 ofNeisseria meningitidis produce sialic acid capsules that are critical in pathogenesis. In each of these serogroups, the capsule transport (ctrABCD) and capsule biosynthesis (synABCD) operons are divergently transcribed from putative promoters located in a 134-bp intergenic region (J. S. Swartley, J. H. Ahn, L. J. Liu, C. M. Kahler, and D. S. Stephens, J. Bacteriol. 178:4052–4059, 1996). In this study we further assessed the role of the intergenic sequence in the transcriptional regulation of the sialic acid capsules of N. meningitidis. Insertional mutagenesis or deletions of the 134-bp sequence in the serogroup B meningococcal strain NMB resulted in a marked reduction or elimination of ctrABCD and synABCDtranscription, with a concomitant loss of encapsulation. Chromosomal transcriptional lacZ-ermC reporter fusions ofsyn and ctr promoters were constructed through allelic exchange. Using these constructs, both operons were found to be constitutively transcribed in meningococci, the biosynthesis operon about fourfold higher than the transport operon. Both promoters showed increased activity during stationary-phase growth. In addition to the promoters, a 70-bp 5′ untranslated region (UTR) upstream ofsynA was found to have a direct repeat and an inverted repeat that overlapped three putative integration host factor binding sites. Mutation of this 70-bp UTR and of the direct repeat upregulated both syn and ctr transcription. Regulation through the synA UTR was absent in a K1 Escherichia coli strain that produces identical capsular polysaccharide, implicating species-specific regulation. Meningococcal sialic acid capsule expression is initiated by divergent promoters in a 134-bp intergenic region, is repressed at the transcriptional level by the 5′ UTR of synA, is increased during stationary-phase growth, and shows species-specific regulation. Transcriptional regulation is another important control point for sialic capsule expression inN. meningitidis.

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Species-specific regulation of angiogenesis by glucocorticoids reveals contrasting effects on inflammatory and angiogenic pathways

PLoS ONE ◽

10.1371/journal.pone.0192746 ◽

2018 ◽

Vol 13 (2) ◽

pp. e0192746 ◽

Cited By ~ 3

Author(s):

Ruth Morgan ◽

John Keen ◽

Daniel Halligan ◽

Alan O’Callaghan ◽

Ruth Andrew ◽

...

Keyword(s):

Specific Regulation ◽

Species Specific

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ABIN-3: a Molecular Basis for Species Divergence in Interleukin-10-Induced Anti-Inflammatory Actions

Molecular and Cellular Biology ◽

10.1128/mcb.00223-07 ◽

2007 ◽

Vol 27 (13) ◽

pp. 4603-4616 ◽

Cited By ~ 39

Author(s):

Brian K. Weaver ◽

Erwin Bohn ◽

Barbi A. Judd ◽

M. Pilar Gil ◽

Robert D. Schreiber

Keyword(s):

Macrophage Activation ◽

Interleukin 10 ◽

Mononuclear Phagocytes ◽

Toll Like Receptor ◽

Monocytic Cells ◽

Proinflammatory Responses ◽

Anti Inflammatory ◽

Species Specific ◽

Anti Inflammatory Cytokine ◽

Necrosis Factor

ABSTRACT Whereas interleukin-10 (IL-10) is an anti-inflammatory cytokine known to regulate macrophage activation, its full mechanism of action remains incompletely defined. In a screen to identify novel IL-10-induced genes, we cloned the mouse ortholog of human ABIN-3 (also termed LIND). ABIN-3 expression was induced selectively by IL-10 in both mouse and human mononuclear phagocytes coordinately undergoing proinflammatory responses. In contrast to the previously characterized ABINs, mouse ABIN-3 was incapable of inhibiting NF-κB activation by proinflammatory stimuli. Generation and analysis of ABIN-3-null mice demonstrated that ABIN-3 is unnecessary for the anti-inflammatory effects of IL-10 as well as for proper negative regulation of NF-κB. Conversely, human ABIN-3 was capable of inhibiting NF-κB activation in response to signaling from Toll-like receptor, IL-1, and tumor necrosis factor. Enforced expression of human ABIN-3 in human monocytic cells suppressed the cytoplasmic degradation of IκBα, the activation of NF-κB, and the induction of proinflammatory genes. Comparative sequence analyses revealed that mouse ABIN-3 lacks a complete ABIN homology domain, which was required for the functional activity of human ABIN-3. ABIN-3 is, thus, an IL-10-induced gene product capable of attenuating NF-κB in human macrophages yet is inoperative in mice and represents a basis for species-specific differences in IL-10 actions.

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