Genome-wide identification of new Wnt/beta-catenin target genes in the human genome using CART method

Abstract : Nowadays the stored information of non-coding human genome regions is being strongly exploited to model the regulation processes. The key to explain complex biological responses, to anticipate and to treat diseases is to understand the regulation factors and the interactions with genes. I summarize the recently published work, developed by C. Hodar, myself, M. Colombres et al. It uses a statistical point of view to study the Wnt pathway that is mainly implicated in cell differentiation, and diseases such as Alzheimer`s (AD) and cancer. We obtain insights on new human genome regions being relevant to control AD or other neurodegenerative disorders. We construct a statistical method based on multiple Classification Trees (CART) to identify new Wnt/beta-catenin pathway target genes, by only using information of known Wnt target (positive) genes and it considers as decision variables the presence of transcription factor binding site motifs in the upstream region of each gene. We propose 89 new Wnt/beta-catenin pathway target genes, we found a group expressed in brain tissue that could be involved in diverse responses to neurodegenerative diseases, like AD. These genes represent new candidates to protect cells against amyloid beta; toxicity, maybe associated to the neuroprotective role of the Wnt signaling pathway and other ones related with cancer. The most relevant were calcium/calmodulin-dependent protein kinase IV (CamK4), with strong evidences for up-regulation in response to both Wnt ligands and lithium, and tropomyosin 1 (alpha) that is associated with neurofibrillary pathology of AD. Our strategy proved to be effective and robust to identify new Wnt/beta-catenin pathway targets. In silico results were biologically validated by RT-qPCR in a sample. Several of the genes represent a new group of transcriptional dependent targets of the canonical Wnt pathway, that could be involved in pathophysiology related to Alzheimer.
Keywords : Wnt Alzheimer CamK4
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https://hal.inria.fr/inria-00541263
Contributeur : Rodrigo Assar <>
Soumis le : mardi 30 novembre 2010 - 11:32:37
Dernière modification le : jeudi 11 janvier 2018 - 06:22:12

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  • HAL Id : inria-00541263, version 1

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Rodrigo Assar, Hodar Christian, Colombres Marcela. Genome-wide identification of new Wnt/beta-catenin target genes in the human genome using CART method. Statistical and dynamical models in biology and medicine, Oct 2010, Heidelberg, Germany. 2010, 〈http://www.ams.med.uni-goettingen.de/modelling_workshop_2010/WorkshopAbstracts.pdf〉. 〈inria-00541263〉

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