J. Thomas

Philip Morris International (Switzerland)

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Manuel C. Peitsch

Philip Morris International (Switzerland)

Nicolas Sierro

Philip Morris International (Switzerland)

Nikolai V. Ivanov

Philip Morris International (Switzerland)

Sonia Ouadi

University of Neuchâtel

James N. D. Battey

Philip Morris International (Switzerland)

Karine Baumer

University of Lausanne

Julia Hoeng

Philip Morris International (Switzerland)

Verena Liedschulte

Philip Morris International (Switzerland)

Lucien Bovet

Philip Morris International (Switzerland)

Hélène Laparra

Philip Morris International (Switzerland)

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Philip Morris International (Switzerland)

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

Toxalim Research Centre in Food Toxicology

Singapore Science Park

Centre National de la Recherche Scientifique

Université Toulouse III - Paul Sabatier

Université de Toulouse

École Nationale Vétérinaire de Toulouse

Institut National de la Recherche Agronomique

Philip Morris International (United States)

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Additional file 2: of The impact of genome evolution on the allotetraploid Nicotiana rustica â an intriguing story of enhanced alkaloid production

Figshare (2018)

Nicolas Sierro James N. D. Battey Lucien Bovet Verena Liedschulte Sonia Ouadi

Table S1. Numbers of NPAMBO, NPAMBE and NUNDSSP repeats in the N. rustica, N. paniculata, N. knightiana and N. undulata genomes. Table S2. Metal accumulations in Nicotiana species in both the greenhouse and field. Table S3. Sequencing libraries for the N. rustica, N. paniculata, N. knightiana and N. undulata genomes. Table S4. Unique proteins from other plant species that map to Nicotiana genomes. Table S5. Transcript length statistics. Table S6. Protein length statistics. (XLSX 39 kb)

10.6084/m9.figshare.7405361

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The effects of cigarette smoke on the intestinal microbiome of mice

F1000Research (2018)

James N. D. Battey Nicolas Sierro Karine Baumer Sonia Ouadi J. Thomas

Open peer review

Intestinal Microbiome

Gut microbiome

10.7490/f1000research.1115605.1

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Comparison of the effects on the ApoE-/- mouse lung epigenome of exposure to the aerosol of a candidate Reduced Risk Product, THS2.2, with exposure to conventional cigarettes smoke

Nicolas Sierro Florian Martin Marja Talikka Sonia Ouadi J. Thomas

Epigenome

10.14869/toxpt.43.1.0_p-126

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The impact of genome evolution on the allotetraploid Nicotiana rustica – an intriguing story of enhanced alkaloid production

BMC Genomics (2018)

Nicolas Sierro James N. D. Battey Lucien Bovet Verena Liedschulte Sonia Ouadi

Nicotiana rustica (Aztec tobacco), like common tobacco (Nicotiana tabacum), is an allotetraploid formed through a recent hybridization event; however, it originated from completely different progenitor species. Here, we report the comparative genome analysis of wild type N. rustica (5 Gb; 2n = 4x = 48) with its three putative diploid progenitors (2.3–3 Gb; 2n = 2x =24), Nicotiana undulata, Nicotiana paniculata and Nicotiana knightiana. In total, 41% of N. rustica genome originated from the paternal donor (N. undulata), while 59% originated from the maternal donor (N. paniculata/N. knightiana). Chloroplast genome and gene analyses indicated that N. knightiana is more closely related to N. rustica than N. paniculata. Gene clustering revealed 14,623 ortholog groups common to other Nicotiana species and 207 unique to N. rustica. Genome sequence analysis indicated that N. knightiana is more closely related to N. rustica than N. paniculata, and that the higher nicotine content of N. rustica leaves is the result of the progenitor genomes combination and of a more active transport of nicotine to the shoot. The availability of four new Nicotiana genome sequences provide insights into how speciation impacts plant metabolism, and in particular alkaloid transport and accumulation, and will contribute to better understanding the evolution of Nicotiana species.

10.1186/s12864-018-5241-5

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Citations (33)

Tobacco Heating System 2.2 has a limited impact on DNA methylation of candidate enhancers in mouse lung compared with cigarette smoke

Food and Chemical Toxicology (2018)

Mohamed-Amin Choukrallah Nicolas Sierro Florian Martin Karine Baumer J. Thomas

Cigarette smoke (CS) exposure has been shown to correlate with changes in DNA methylation levels, however, the impact of CS on DNA methylation at genome-wide scale is missing. Here, we used whole-genome bisulfite sequencing to assess the effects of CS extract and aerosol from the Tobacco Heating System (THS) 2.2, a candidate modified risk tobacco product, on DNA methylation in lung and liver tissues from apolipoprotein E-deficient mice during an eight-month period of exposure. We found that in lung tissue, CS mainly induced hypermethylation of candidate enhancers at late time points, while promoters were less affected. This effect was strongly reduced upon cessation or switching to THS 2.2. By contrast, chronic exposure to THS 2.2 had a limited effect on DNA methylation at both promoters and enhancers. We also identified members of the Ets and Fox families of transcription factors as potential players in the epigenetic response to CS exposure in lung tissue. In contrast to the lung, DNA methylation in the liver was largely insensitive to all investigated exposures. In summary, our investigations indicate that CS-related DNA methylation alterations are tissue-specific, occur mainly at enhancers and are strongly reduced upon smoking cessation or switching to THS2.2.

Bisulfite sequencing

Tobacco smoke

Epigenomics

10.1016/j.fct.2018.11.020

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Citations (12)

Intracellular receptors use a common mechanism to interpret signaling information at response elements.

Genes & Development (1996)

D. Barry Starr William Matsui J. Thomas Keith R. Yamamoto

The glucocorticoid receptor (GR) activates transcription in certain glucocorticoid response element (GRE) contexts, and represses or displays no activity in others. We isolated point mutations in one GRE, plfG, at which GR activated transcription under conditions in which the wild-type element was inactive or conferred repression, implying that GREs may carry signals that are interpreted by bound receptors. Consistent with this notion, we identified a mutant rat GR, K461A, which activated transcription in all GRE contexts tested, implying that this residue is important in interpretation of GRE signals. In a yeast screen of 60,000 GR mutants for strong activation from plfG, all 13 mutants isolated contained substitutions at K461. This lysine residue is highly conserved in the zinc-binding region (ZBR) of the intracellular receptor (IR) superfamily; when it was mutated in MR and RARbeta, the resulting receptors similarly activated transcription at response elements that their wild-type counterparts repressed or were inactive. We suggest that IR response elements serve in part as signaling components, and that a critical lysine residue serves as an allosteric "lock" that restricts IRs to inactive or repressing configurations except in response element contexts that signal their conversion to transcriptional activators. Therefore, mutation of this residue produces altered receptors that activate in many or all response element contexts.

Transcription

Response element

Hormone response element

10.1101/gad.10.10.1271

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Citations (125)

A role for HDJ-2/HSDJ in correcting subnuclear trafficking, transactivation, and transrepression defects of a glucocorticoid receptor zinc finger mutant.

Molecular Biology of the Cell (1997)

Yuting Tang Charu Ramakrishnan J. Thomas Donald Defranco

All steroid receptors possess a bipartite nuclear localization signal sequence (NLS) that localizes within the second zinc finger of their DNA-binding domain. Fine-structure mapping of the rat glucocorticoid receptor (rGS) NLS identified a composite signal composed of three distinct proto-NLSs that function effectively when present in unique pairs. At least one of the rGR proto-NLSs appears to influence receptor trafficking within the nucleus, as revealed by a unique nuclear staining pattern of receptors possessing a point mutation (i.e., arginine at position 496; R496), at proto-NLS, pNLS-2. Specifically, carboxyl-terminal-truncated rGRs possessing various point mutations at R496 localized within a limited number of large foci in nuclei of transiently transfected COS-1 cells. R496 mutations did not affect subnuclear targeting when present in full-length rGR, reflecting a protective effect of the receptor's ligand-binding domain that can be exerted in cis and in trans. The effects of rGR R496 mutations on subnuclear targeting were not autonomous because we also observed a coincident localization of hsp70, the 70-kDa heat shock protein, within nuclear foci that include r496 mutant receptors. The elimination of R496 mistargeting by overexpression of an hsp70 partner (i.e., the DnaJ homologue, HDJ-2/HSDJ) suggests that the hsp70/DnaJ chaperone system is mobilized to specific sites within the nucleus in response to inappropriate targeting or folding of specific mutant receptors. HDJ-2/HSDJ overexpression also corrects defective transactivation and transrepression activity of R496 mutant GRs. Thus, molecular chaperones, such as members of the hsp70 and DnaJ families, may survey the nucleus for misfolded proteins and actively participate in their refolding into biologically active conformational states.

Transrepression

Karyopherin

10.1091/mbc.8.5.795

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Citations (59)

Additional file 7: of The impact of genome evolution on the allotetraploid Nicotiana rustica â an intriguing story of enhanced alkaloid production

Figshare (2018)

Nicolas Sierro James N. D. Battey Lucien Bovet Verena Liedschulte Sonia Ouadi

File S1. Protein sequences of the genes and key regulators of the alkaloid pathway. (TXT 90 kb)

10.6084/m9.figshare.7405415

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Epigenetic regulation of protein: DNA interactions on UTE-1: A novel and essential regulatory element in the human TIMP-1 gene promoter

Journal of Hepatology (2000)

Derek A. Mann Julie E. Trim Narendra Mungalsingh J. Thomas M J Arthur

10.1016/s0168-8278(00)80641-8

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Impact of 6-Month Exposure to Aerosols From Potential Modified Risk Tobacco Products Relative to Cigarette Smoke on the Rodent Gastrointestinal Tract

Frontiers in Microbiology (2021)

James N. D. Battey Justyna Szostak Blaine Phillips Charles Teng Ching Keong Tung

Cigarette smoking causes adverse health effects that might occur shortly after smoking initiation and lead to the development of inflammation and cardiorespiratory disease. Emerging studies have demonstrated the role of the intestinal microbiome in disease pathogenesis. The intestinal microbiome is susceptible to the influence of environmental factors such as smoking, and recent studies have indicated microbiome changes in smokers. Candidate modified risk tobacco products (CMRTP) are being developed to provide substitute products to lower smoking-related health risks in smokers who are unable or unwilling to quit. In this study, the ApoE –/– mouse model was used to investigate the impact of cigarette smoke (CS) from the reference cigarette 3R4F and aerosols from two CMRTPs based on the heat-not-burn principle [carbon-heated tobacco product 1.2 (CHTP 1.2) and tobacco heating system 2.2 (THS 2.2)] on the intestinal microbiome over a 6-month period. The effect of cessation or switching to CHTP 1.2 after 3 months of CS exposure was also assessed. Next-generation sequencing was used to evaluate the impact of CMRTP aerosols in comparison to CS on microbiome composition and gene expression in the digestive tract of mice. Our analyses highlighted significant gene dysregulation in response to 3R4F exposure at 4 and 6 months. The findings showed an increase in the abundance of Akkermansiaceae upon CS exposure, which was reversed upon cessation. Cessation resulted in a significant decrease in Akkemansiaceae abundance, whereas switching to CHTP 1.2 resulted in an increase in Lactobacillaceae abundance. These microbial changes could be important for understanding the effect of CS on gut function and its relevance to disease pathogenesis via the microbiome.

Tobacco smoke

10.3389/fmicb.2021.587745

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Citations (8)