References of "Pendeville-Samain, Hélène"
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See detailUnderstanding angiogenesis through novel epigenetic modulators
Shiva Shankar, Thammadihalli Veerasangaiah ULg; Sulka, Béatrice; Blacher, Silvia ULg et al

Scientific conference (2012, June 22)

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA ... [more ▼]

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA methyltransferases (DNMT) inhibitors are potent anti-angiogenic compounds. Though combination of HDAC and DNMT inhibitors are now being examined in clinical trials of hematological malignancies, little work has been done to understand the effect of this combination on physiological and tumoral angiogenesis. We have designed and tested a family of twin drugs with intrinsic HDAC and DNMT inhibitory activities in relevant models of angiogenesis in vitro (Human Umbilical Vein Endothelial Cells – HUVEC and aortic ring) and in vivo (chick chorioallantoic membrane and Zebrafish). We have identified a lead compound having quantifiable anti-angiogenic effect without cytotoxicity affecting global histone acetylation and DNA methylation levels. In order to elucidate its anti-angiogenic mechanism, we characterized gene expression pattern simultaneously with the methylation profile of HUVEC cells treated with the lead compound and reference epigenetic modulators. This approach based on parallel microarray analyses permitted us to underscore a list of genes exclusively affected by the lead compound but not by other HDAC or DNMT inhibitors. These genes were then analyzed using the Ingenuity Pathway software revealing potential involvement of a subset of genes in angiogenesis. Our present work is focused on exploring the exact role of these genes on angiogenesis using RNA silencing and vectors cloned with genes of interest. We are using these novel epigenetic modulators as a tool to understand the regulatory mechanism of angiogenesis and to develop effective approaches to treat cancer. [less ▲]

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See detailNovel HDAC/DNMT Twin inhibitors interfere with angiogenesis
Shiva Shankar, Thammadihalli Veerasangaiah ULg; Sulka, Béatrice ULg; Blacher, Silvia ULg et al

Poster (2011, January 31)

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA ... [more ▼]

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA methyltransferases (DNMT) inhibitors are potent anti-angiogenic compounds. Though combination of HDAC and DNMT inhibitors are now being examined in clinical trials of hematological malignancies, little work has been done to understand the effect of this combination on physiological and tumoral angiogenesis. We have designed and tested a family of twin drugs with intrinsic HDAC and DNMT inhibitory activities in relevant models of angiogenesis in vitro (Human Umbilical Vein Endothelial Cells – HUVEC and aortic ring) and in vivo (chick chorioallantoic membrane and Zebrafish). We have identified a lead compound having quantifiable anti-angiogenic effect without cytotoxicity affecting global histone acetylation and DNA methylation levels. In order to elucidate its anti-angiogenic mechanism, we characterized gene expression pattern simultaneously with the methylation profile of HUVEC cells treated with the lead compound and reference epigenetic modulators. This approach based on parallel microarray analyses permitted us to underscore a list of genes exclusively affected by the lead compound but not by other HDAC or DNMT inhibitors. These genes were then analyzed using the Ingenuity Pathway software revealing potential involvement of a subset of genes in angiogenesis. Our present aim is to validate the expression levels of a series of genes with respect to epigenetic mechanisms (histone modifications and DNA methylation). Finally, the biological relevance of the target genes will be explored by RNA silencing. Hence, we are using these novel epigenetic modulators as a tool to understand the regulatory mechanism of angiogenesis and to develop effective approaches to treat cancer. [less ▲]

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See detailZebrafish Sox7 and Sox18 function together to control arterial-venous identity
Pendeville-Samain, Hélène ULg; Winandy, Marie ULg; Manfroid, Isabelle ULg et al

in Developmental Biology (2008), 317(2), 405-16

Sox7 and Sox18 are members of the F-subgroup of Sox transcription factors family and are mostly expressed in endothelial compartments. In humans, dominant mutations in Sox18 are the underlying cause of ... [more ▼]

Sox7 and Sox18 are members of the F-subgroup of Sox transcription factors family and are mostly expressed in endothelial compartments. In humans, dominant mutations in Sox18 are the underlying cause of the severe hypotrichosis-lymphedema-telangiectasia disorder characterized by vascular defects. However little is known about which vasculogenic processes Sox7 and Sox18 regulate in vivo. We cloned the orthologs of Sox7 and Sox18 in zebrafish, analysed their expression pattern and performed functional analyses. Both genes are expressed in the lateral plate mesoderm during somitogenesis. At later stages, Sox18 is expressed in all axial vessels whereas Sox7 expression is mainly restricted to the dorsal aorta. Knockdown of Sox7 or Sox18 alone failed to reveal any phenotype. In contrast, blocking the two genes simultaneously led to embryos displaying dysmorphogenesis of the proximal aorta and arteriovenous shunts, all of which can account for the lack of circulation observed in the trunk and tail. Gene expression analyses performed with general endothelial markers on double morphants revealed that Sox7 and Sox18 are dispensable for the initial specification and positioning of the major trunk vessels. However, morphants display ectopic expression of the venous Flt4 marker in the dorsal aorta and a concomitant reduction of the artery-specific markers EphrinB2a and Gridlock. The striking similarities between the phenotype of Sox7/Sox18 morphants and Gridlock mutants strongly suggest that Sox7 and Sox18 control arterial-venous identity by regulating Gridlock expression. [less ▲]

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See detailThe ornithine decarboxylase gene is essential for cell survival during early murine development
Pendeville-Samain, Hélène ULg; Carpino, Nick; Marine, Jean-Christophe et al

in Molecular & Cellular Biology (2001), 21(19), 6549-58

Overexpression and inhibitor studies have suggested that the c-Myc target gene for ornithine decarboxylase (ODC), the enzyme which converts ornithine to putrescine, plays an important role in diverse ... [more ▼]

Overexpression and inhibitor studies have suggested that the c-Myc target gene for ornithine decarboxylase (ODC), the enzyme which converts ornithine to putrescine, plays an important role in diverse biological processes, including cell growth, differentiation, transformation, and apoptosis. To explore the physiological function of ODC in mammalian development, we generated mice harboring a disrupted ODC gene. ODC-heterozygous mice were viable, normal, and fertile. Although zygotic ODC is expressed throughout the embryo prior to implantation, loss of ODC did not block normal development to the blastocyst stage. Embryonic day E3.5 ODC-deficient embryos were capable of uterine implantation and induced maternal decidualization yet failed to develop substantially thereafter. Surprisingly, analysis of ODC-deficient blastocysts suggests that loss of ODC does not affect cell growth per se but rather is required for survival of the pluripotent cells of the inner cell mass. Therefore, ODC plays an essential role in murine development, and proper homeostasis of polyamine pools appears to be required for cell survival prior to gastrulation. [less ▲]

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See detailFunctional analysis of ZNF85 KRAB zinc finger protein, a member of the highly homologous ZNF91 family
Poncelet, Dominique A.; Bellefroid, Eric J.; Bastiaens, P. V. et al

in DNA & Cell Biology (1998), 17(11), 931-43

We previously identified the ZNF85 (HPF4) KRAB zinc finger gene, a member of the human ZNF91 family. Here, we show that the ZNF85 gene is highly expressed in normal adult testis, in seminomas, and in the ... [more ▼]

We previously identified the ZNF85 (HPF4) KRAB zinc finger gene, a member of the human ZNF91 family. Here, we show that the ZNF85 gene is highly expressed in normal adult testis, in seminomas, and in the NT2/D1 teratocarcinoma cell line. Immunocytochemical localization of a panel of beta-Gal/ZNF85 fusion proteins revealed that ZNF85 contains at least one nuclear localization signal located in the spacer region connecting the KRAB domain with the zinc finger repeats. Bacterially expressed ZNF85 zinc finger domain bound strongly and exclusively to DNA in vitro in a zinc-dependent manner. The KRAB(A) domain of the ZNF85 protein and of several other members of the ZNF91 family exhibited repressing activity when tested in Gal4 fusion protein assays. The repression was significantly enhanced by the addition of the KRAB (B) domain, whereas further addition of other conserved regions had no effect. The ZNF85 KRAB(A) and (B) domains in vitro bound several nuclear proteins that might constitute critical cofactors for repression. [less ▲]

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See detailRégulation transcriptionnelle du gène de la prolactine humaine
Muller, Marc ULg; Berwaer, Monique; Caccavelli, Laure et al

in Medecine Sciences : M/S (1998), 14(580-587),

Le gène humain de la prolactine (hPRL) est exprimé essentiellement par l'antéhypophyse. L'analyse des éléments régulateurs de la transcription sur plus de 5 000 bases en amont du site de début de ... [more ▼]

Le gène humain de la prolactine (hPRL) est exprimé essentiellement par l'antéhypophyse. L'analyse des éléments régulateurs de la transcription sur plus de 5 000 bases en amont du site de début de transcription a montré l'importance du contrôle par le facteur de transcription Pit-1, spécifique de l'hypophyse, à côté de facteurs ubiquistes. Des hormones modulent l'expression du gène hPRL, transmettant leur signal par les voies intracellulaires de l'AMP cyclique et du calcium, relayées au niveau du promoteur proximal (-250/+1) essentiellement par les facteurs de transcription Pit-1 et AP-1. Les récepteurs nucléaires contrôlent aussi en partie la transcription de hPRL: le récepteur des oestrogènes l'active en se liant aux éléments de réponse distaux ; les récepteurs nucléaires des hormones thyroïdiennes et des glucocorticoïdes la répriment en interférant respectivement avec la fonction activatrice de AP-1 et de Pit-1. [less ▲]

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See detailA role for Xenopus Gli-type zinc finger proteins in the early embryonic patterning of mesoderm and neuroectoderm
Marine, Jean-Christophe; Bellefroid, Eric J.; Pendeville-Samain, Hélène ULg et al

in Mechanisms of Development (1997), 63(2), 211-25

Gli-type zinc finger proteins play important regulatory roles in vertebrate and invertebrate embryogenesis. In Xenopus, the Gli-type proteins XGli-3 and XGli-4 are first expressed in earliest stages of ... [more ▼]

Gli-type zinc finger proteins play important regulatory roles in vertebrate and invertebrate embryogenesis. In Xenopus, the Gli-type proteins XGli-3 and XGli-4 are first expressed in earliest stages of mesoderm and neural development. Transient transfection assays reveal that XGli-3 and XGli-4 can function as transcription repressors. Counteracting the Gli-protein repressor activity by ectopic expression of a fusion protein that contains the Gli-zinc finger cluster connected to the E1A activator domain in Xenopus embryos results in specific morphological alterations in the developing somites and in the central nervous system. Altered expression characteristics for a broad set of molecular markers highlighting specific aspects of mesodermal and neural differentiation demonstrate an important role for Gli-type zinc finger proteins in the early mesodermal and neural patterning of Xenopus embryos. [less ▲]

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