Pascal GP Martin

Indiana University Bloomington | IUB · Department of Biology

Ensuring that one gene's transcription does not inappropriately affect the expression of its neighbors is a fundamental challenge to gene regulation in a genomic context. In plants, which lack homologs of animal insulator proteins, the mechanisms that prevent transcriptional interference are not well understood. Here we show that BORDER proteins ar...

Unlabelled: Changes in lifestyle are suspected to have strongly influenced the current obesity epidemic. Based on recent experimental, clinical, and epidemiological work, it has been proposed that some food contaminants may exert damaging effects on endocrine and metabolic functions, thereby promoting obesity and associated metabolic diseases such...

Fipronil is described as a thyroid disruptor in rat. Based on the hypothesis that this results from a perturbation of hepatic thyroid hormone metabolism, our goal was to investigate the pathways involved in fipronil-induced liver gene expression regulations. First, we performed a microarray screening in the liver of rats treated with fipronil or ve...

In mammals, birth entails complex metabolic adjustments essential for neonatal survival. Using a mouse knockout model, we identify crucial biological roles for the miR-379/miR-410 cluster within the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 locus, also named C14MC in humans, is the largest known placental mamm...

Glucocorticoids (GCs) contribute to human intestine ontogeny and accelerate gut barrier development in preparation to birth. In comparison, the rat gut is immature at birth, and high intestinal GCs sensitivity during the first two weeks of life resembles that of premature infants. This makes suckling rats a model to investigate postpartum impact of...

Transcription initiation has long been considered a primary regulatory step in gene expression. Recent work, however, shows that downstream events, such as transcription elongation, can also play important roles.1, 2, 3 A well-characterized example from animals is promoter-proximal pausing, where transcriptionally engaged Pol II accumulates 30–50 b...

Food and feed can be naturally contaminated by several mycotoxins, and concern about the hazard of exposure to mycotoxin mixtures is increasing. In this study, more than 800 metabolites were analyzed in 524 finished pig feed samples collected worldwide. Eighty-eight percent of the samples were co-contaminated with deoxynivalenol (DON) and other reg...

Fipronil is a phenylpyrazole insecticide used for the control of a variety of pest for domestic, veterinary and agricultural uses. Fipronil exposure is associated to thyroid disruption in the rat. It increases thyroid hormone (TH) hepatic clearance. The effect on thyroxine (T4) clearance is about four fold higher than the effect on T4 plasma concen...

The extraction of RNA and lipids from a large number of biological samples is time-consuming and costly with steps required for both transcriptomic and lipidomic approaches. Most protocols rely on independent extraction of nucleic acids and lipids from a single sample, thereby increasing the need for biological material and inducing variability in...

Olive oil consumption is beneficial for health as it is associated with a decreased prevalence of cancer and cardiovascular diseases. Oleic acid is, by far, the most abundant component of olive oil. Since it can be made through de novo synthesis in animals, it is not an essential fatty acid. While it has become clear that dietary oleic acid regulat...

Diets composition. (DOCX)

Fatty acids were analyzed by gas chromatography. Data are the mean of the masse percentage measured in liver of LXR+/+ and LXR-/- mice fed the REF or the OLIV diet. a Significant genotype effect. b Significant difference versus REF diet. (n = 6 animals per group). (DOCX)

Triolein promotes lipogenic gene expression in vivo. Hepatic Acaca, Fasn, Elovl6, Scd1 and Cyp4a14 mRNA levels quantified by qPCR. Data are the mean ± SEM of values measured in C57Bl/6J fed fat free diet and daily gavaged with triolein (TRIOL), the same olive oil we used in the OLIV diet (OLIV), a mix of theses two oils (OLIV/TRIOL) and a mix of OL...

Relative fatty acid composition of dietary oils (%). (DOCX)

Oleate does not induce LXR target genes in vitro. mRNA expression of Fatty acid synthase (Fasn) and Stearoyl-CoA Desaturase 1 (Scd1) measured by qPCR in Hepa1 cells (A) and in Mouse embryonnic fibroblast (B) treated with TO901317 or with Oleic Acid (OA) provided as an albuminic complex. Values are means ± SEM (n = 3), *: Significant (p<0,05) effect...

Oligonucleotide sequences for real time PCR. (DOCX)

Quantification of cytoplasmic and nuclear proteins presented in Fig 3. (A) Cytoplasmic ACLY, P-ACLY, ACC, FAS, ELOVL6, SCD1, SREBP-1 and ChREBP protein quantification. (B) Nuclear SREBP-1, ChREBP and LXR protein quantification. Values are mean ± SEM (n = 6); a Significant gentotype effect. b Significant difference versus REF diet. (TIF)

Alterations in NO availability and signaling play a pivotal role at early stages of the metabolic syndrome (MetSynd). We hypothesized that dietary α-linolenic acid (ALA, 18:3 n-3) favors NO availability by modulating amino acid metabolism, with a specific impact on the arginine–NO pathway. Mice were fed a hyperlipidic diet (285 g lipid/kg, 51.1 % e...

Among transcriptomic studies, those comparing species or populations can increase our understanding of the impact of the evolutionary forces on the differentiation of populations. A particular situation is the one of short evolution time with breeds of a domesticated species that underwent strong selective pressures. In this study, the gene express...

RNA editing is a post-transcriptional process leading to differences between genomic DNA and transcript sequences, potentially enhancing transcriptome diversity. With recent advances in high-throughput sequencing, many efforts have been made to describe mRNA editing at the transcriptome scale, especially in mammals, raising contradictory conclusion...

Free fatty acid receptors (FFAR) belong to a family of five G-Protein Coupled Receptors that are involved in the regulation of lipid metabolism, so that their loss of function increases the risk of obesity. The aim of this study was to determine the expansion of genes encoding paralogs of FFAR2 in the chicken, considered as a model organism for dev...

Core packages and functions for the analysis of NGS data with Bioconductor.

RNA polymerase II (RNAPII) pausing/termination shortly after initiation is a hallmark of gene regulation. Here, we show that negative elongation factor (NELF) interacts with Integrator complex subunits (INTScom), RNAPII and Spt5. The interaction between NELF and INTScom subunits is RNA and DNA independent. Using both human immunodeficiency virus ty...

Bisphenol A (BPA) is a suspected endocrine disruptor highly prevalent in our environment since it is used as monomer of polycarbonate plastics and epoxy resins. Recent epidemiological and animal studies have suggested that BPA exposure may influence the development of obesity and related pathologies such as type 2 diabetes and cardiovascular diseas...

Background In pigs, the perinatal period is the most critical time for survival. Piglet maturation, which occurs at the end of gestation, leads to a state of full development after birth. Therefore, maturity is an important determinant of early survival. Skeletal muscle plays a key role in adaptation to extra-uterine life, e.g. glycogen storage and...

Abstract Text: Genetic progress on litter size is often accompanied by a rise of piglet mortality. The most critical time for survival is the perinatal period. Piglet maturation occurs at the end of gestation between 90 and 110 days. Maturity is an important determinant of early survival. The skeletal muscle, via glycogen storage, plays a key rol...

Abstract Text: Crossbred piglets from Large White sows showed faster early development as compared to their purebred counterparts (P<0.01). In Meishan sows, crossbred females were heavier than purebred females from d1 on, but no difference in relative growth rate was found between purebreds and crossbreds. Piglet growth and behaviour traits related...

Glucocorticoids (GC) contribute to human intestine ontogeny and accelerate gut barrier development in preparation to birth. Rat gut is immature at birth, and high intestinal GC sensitivity during the first two weeks of life resembles that of premature infants. This makes suckling rats a model to investigate postpartum impact of maternal separation...

Eukaryotic chromosomes are partitioned into topologically associating domains (TADs) that are demarcated by distinct insulator-binding proteins (IBPs) in Drosophila. Whether IBPs regulate specific long-range contacts and how this may impact gene expression remains unclear. Here we identify "indirect peaks" of multiple IBPs that represent their dist...

Background: Prader-Willi syndrome (PWS) results from abnormalities in the genomic imprinting process leading to hypothalamic dysfunction with an alteration of growth hormone (GH) secretion. PWS is associated with early morbid obesity and short stature which can be efficiently improved with GH treatment. Objectives: Our aims were to highlight adi...

PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal 3-keto-acyl-CoA thiolase B (Thb) is under the dependence of these two transcription factors. Transactivation and gel shift...

Background & aims: Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. Methods: We used wild type mice and mice lacking Liver X Recept...

Fructose consumption is associated with the development of obesity and metabolic diseases. In mouse, high fructose diet consumption induces the expression of genes involved in lipogenesis and hepatic triglyceride accumulation. While it is clear that such steatosis occurs as a consequence of change in lipogenic gene expression, the exact mechanisms...

The Liver X Receptors (LXRs) α and β and the peroxisome proliferator-activated receptor α (PPARα) are transcription factors that belong to class II nuclear receptors. They drive the expression of genes involved in hepatic lipid homeostasis and therefore are important targets for the prevention and treatment of nonalcoholic fatty liver disease (NAFL...

Intestinal permeability (IP) is high at birth for maturation of gut barrier function and liver development. In neonate rats, it is well established that chronic maternal deprivation for 12-14 days induces long-term defect in IP in adulthood. In human newborns, transient maternal separation (MS) is common practice, mainly when medical care is requir...

In rats, the widely used insecticide fipronil increases the clearance of thyroxine (T(4)). This effect is associated with a high plasma concentration of fipronil sulfone, the fipronil main metabolite in several species including rats and humans. In sheep, following fipronil treatment, fipronil sulfone plasma concentration and thyroid disruption are...

In rats, the widely used insecticide fipronil increases the clearance of thyroxine (T-4). This effect is associated with a high plasma concentration of fipronil sulfone, the fipronil main metabolite in several species including rats and humans. In sheep, following fipronil treatment, fipronil sulfone plasma concentration and thyroid disruption are...

Although the main role of P-glycoprotein (Pgp) is to extrude a broad range of xenochemicals and to protect the organism against xenotoxicity, it also transports a large range of endogenous lipids. Using mice lacking Pgp, we have investigated the possible involvement of Pgp in lipid homeostasis in vivo. In a long term study, we have followed the foo...

Glutathione (GSH) derives from cysteine and plays a key role in redox status. GSH synthesis is determined mainly by cysteine availability and γ-glutamate cysteine ligase (γGCL) activity. Because PPARα activation is known to control the metabolism of certain amino acids, GSH synthesis from cysteine and related metabolisms were explored in wild-type...

Changes in the nuclear positioning of specific genes, depending on their expression status, have been observed in a large diversity of physiological processes. However, gene position is poorly documented for immune cells which have been subjected to activation following bacterial infection. Using a pig model, we focused our study on monocyte-derive...

De novo fatty acid biosynthesis is also called lipogenesis. It is a metabolic pathway that provides the cells with fatty acids required for major cellular processes such as energy storage, membrane structures and lipid signaling. In this article we will review the role of the Liver X Receptors (LXRs), nuclear receptors that sense oxysterols, in the...

Although the main role of P-glycoprotein (Pgp) is to extrude a broad range of xenochemicals and to protect the organismagainst xenotoxicity, it also transports a large range of endogenous lipids. Using mice lacking Pgp, we have investigated thepossible involvement of Pgp in lipid homeostasis in vivo. In a long term study, we have followed the food...

PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal 3-keto-acyl-CoA thiolase B (Thb) is under the dependence of these two transcription factors. Transactivation and gel shift...

Review discusses recent findings on the role of FAN, a TNF receptor 1 adaptor protein, in TNFα-induced cell signaling and biological responses. TNF-α is a pleiotropic cytokine involved in the regulation of various biological effects, including cell survival and proliferation, cell differentiation, and cell death. Moreover, TNF-α triggers proinflamm...

The pleiotropic effects of PPARα may include the regulation of amino acid metabolism. Nitric oxide (NO) is a key player in vascular homeostasis. NO synthesis may be jeopardized by a differential channeling of arginine toward urea (via arginase) versus NO (via NO synthase, NOS). This was studied in wild-type (WT) and PPARα-null (KO) mice fed diets c...

Apelin, an adipocyte-secreted factor upregulated by insulin, is increased in adipose tissue (AT) and plasma with obesity. Apelin was recently identified as a new player in the control of glucose homeostasis. However, the regulation of apelin and APJ (apelin receptor) expression in skeletal muscle in relation to insulin resistance or type 2 diabetes...

In cattle fattening, the illicit use of growth promoters (GPs) represents a major problem. The synthetic corticosteroid dexamethasone (DEX) is the GP mostly used, alone or in combination with other steroids or beta-agonists. Recently, GPs were shown to disrupt some cattle cytochromes P450 (CYPs) at the post-transcriptional level; therefore, the eff...

In mammalian cells, elongases and desaturases play critical roles in regulating the length and degree of unsaturation of fatty acids and thereby their functions and metabolic fates. In the past decade, a great deal has been learnt about these enzymes and the first part of this review summarizes our current knowledge concerning these enzymes. More r...

Bisphenol A (BPA), a chemical estrogen widely used in the food-packaging industry and baby bottles, is recovered in human fluids (0.1-10 nM). Recent studies have reported that BPA is hormonally active at low doses, emphasizing the debate of a risk for human health. Estrogen receptors are expressed in the colon, and although the major route of BPA e...

Factor associated with neutral sphingomyelinase activation (FAN) is an adaptor protein that constitutively binds to TNF-R1. Microarray analysis was performed in fibroblasts derived from wild-type or FAN knockout mouse embryos to evaluate the role of FAN in TNF-induced gene expression. Approximately 70% of TNF-induced genes exhibited lower expressio...

The purpose of this study is to identify the hierarchy of importance amongst pathways involved in fatty acid (FA) metabolism and their regulators in the control of hepatic FA composition. A modeling approach was applied to experimental data obtained during fasting in PPARalpha knockout (KO) mice and wild-type mice. A step-by-step procedure was used...