Ivo Teneng - Academia.edu (original) (raw)

Papers by Ivo Teneng

Http Dx Doi Org 10 1089 Cmb 2006 0125, May 1, 2007

We present a methodology aimed at partial validation and accuracy-precision assessment of a mathe... more We present a methodology aimed at partial validation and accuracy-precision assessment of a mathematical model of gene transcription at the cellular level. The method is based on the analysis of time-series measurements aggregated over a large number of cells. Such measurements are typically obtained via reverse transcriptase-polymerase chain reaction (RT-PCR) experiments. The validation procedure presented herein uses as an example data on L1 retrotransposon gene in HeLa cells. The procedure compares model predicted values with the RT-PCR data for L1 by means of the standard Bayesian statistical techniques with the help of modern Markov-Chain Monte-Carlo methodology.

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2007

Injury to the cellular components of the vascular wall and blood by endogenous and exogenous chem... more Injury to the cellular components of the vascular wall and blood by endogenous and exogenous chemicals has been associated with atherosclerosis in humans and experimental systems. The genetic and molecular mechanisms responsible for initiation and promotion of atherosclerotic changes include modulation of extracellular matrix-integrin axis, genes involved in the regulation of growth and differentiation and possibly, genomic stability. This review summarizes seminal studies over the past 20 years that shed light on critical gene-gene and gene-environment interactions mediating the atherogenic response to chemical injury.

Epigenetics and Human Health, 2013

ABSTRACT Transposable elements such as LINE-1 (long interspersed nuclear element-1 or L1) are mob... more ABSTRACT Transposable elements such as LINE-1 (long interspersed nuclear element-1 or L1) are mobile genetic moieties within the genome. L1 retrotransposons comprise 21 % of the human genome by mass, and up to 100 are believed to remain retrotransposition competent within the human genome. During embryonic development, the genome undergoes reprogramming events defined by specific patterns of DNA methylation established de novo after implantation and preferentially targeted to repetitive sequences. Recent studies in the Ramos laboratory have shown that the ability of polycyclic aromatic hydrocarbon carcinogens, such as benzo(a)pyrene, to reactivate L1 transcription and retrotransposition in mammalian cells involves dysregulation of epigenetic programming mediated in part via mechanisms involving the aryl hydrocarbon receptor, a ligand-activated transcription factor and regulator of several other biological processes. The most detrimental effect of L1 on the genome is believed to be insertion into functional sequences that severely compromise gene function. Other studies have shown that L1 reactivation mediates changes in genetic programming of differentiation networks. Because L1 insertions can have a profound impact on primary genetic structure as well as epigenetic status of the host, they represent ideal molecular targets for development of novel epigenetic therapies targeting medical conditions that involve derangements of L1 activity. Loading...

Journal of Computational Biology, 2007

Journal of Biological Chemistry, 2007

Genes to Cells, 2007

The present study was conducted to evaluate the contextual specificity of long interspersed nucle... more The present study was conducted to evaluate the contextual specificity of long interspersed nuclear element-1 (LINE-1 or L1) activation by cellular stress and the role of the aryl hydrocarbon receptor (AHR) transcription factor and oxidative stress in the gene activation response. Activation of the AHR by the genotoxic carcinogen benzo(a)pyrene (BaP) increased L1 expression in human cervical carcinoma (HeLa) cells, human microvascular endothelial cells (HMEC), mouse vascular smooth muscle cells (mVSMC) and mouse embryonic kidney cells (mK4). In contrast, challenge with a different AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or UV irradiation (10-20 J/m 2), induced L1 only in HeLa cells. Transactivation of the mouse L1Md-A5 promoter was observed in all cell types challenged with BaP, while TCDD was without effect, and UV only activated L1 in HeLa cells. Genetic and pharmacological experiments implicated the AHR and oxidative stress as contextual determinants of L1 inducibility by cellular stress.

Birth Defects Research Part A: Clinical and Molecular Teratology, 2011

Background-L1 retroelements may play a central role in morphogenesis through epigenetic mechanism... more Background-L1 retroelements may play a central role in morphogenesis through epigenetic mechanisms involving recruitment of chromatin modifying protein complexes. Retroelements are repressed in terminally differentiated cells, and highly active in embryonic, undifferentiated, and transformed cells. It is not clear if the modulation of differentiation by L1 is a "cause" or "effect". The aim of this study was to determine if murine embryonic kidney cells of clonal origin (mK4 cells) harbor retrotransposition events upon ectopic expression of L1, and the impact of L1 on embryonic kidney cell differentiation. Given that L1 is reactivated by AHR ligands, we also sought to investigate the effects of benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the genetic network of mK4 cells. Methods-mK4 cells overexpressing human LI RP were assessed for changes in proliferation and expression of molecular markers of cellular differentiation. Results-L1 RP increased proliferation rates and markedly downregulated differentiation programming in mK4 cells. These genetic alterations were recapitulated by exogenous activation of L1 by AHR ligands. Conclusion-L1 regulates nephrogenesis in vitro via both insertional and non-insertional mechanisms that disrupt mesenchymal to epithelial transition. Thus, a feedback loop involving L1, WT1 and AHR may play a role in regulation of kidney morphogenesis.

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2009

Long interspersed nuclear elements (LINEs or L1 elements) are targeted for epigenetic silencing d... more Long interspersed nuclear elements (LINEs or L1 elements) are targeted for epigenetic silencing during early embryonic development and remain inactive in most cells and tissues. Here we show that E2F-Rb family complexes participate in L1 elements epigenetic regulation via nucleosomal histone modifications and recruitment of histone deacetylases (HDACs) HDAC1 and HDAC2. Our experiments demonstrated that (i) Rb and E2F interact with human and mouse L1 elements, (ii) L1 elements are deficient in both heterochromatin-associated histone marks H3 tri methyl K9 and H4 tri methyl K20 in Rb family triple knock out (Rb, p107, and p130) fibroblasts (TKO), (iii) L1 promoter exhibits increased histone H3 acetylation in the absence of HDAC1 and HDAC2 recruitment, (iv) L1 expression in TKO fibroblasts is upregulated compared to wild type counterparts, (v) L1 expression increases in the presence of the HDAC inhibitor TSA. On the basis of these findings we propose a model in which L1 sequences throughout the genome serve as centers for heterochromatin formation in an Rb family-dependent manner. As such, Rb proteins and L1 elements may play key roles in heterochromatin formation beyond pericentromeric chromosomal regions. These findings describe a novel mechanism of L1 reactivation in mammalian cells mediated by failure of corepressor protein recruitment by Rb, loss of histone epigenetic marks, heterochromatin formation, and increased histone H3 acetylation.