ation Research, University of North Carolina-Chapel Hill, 27514 Chapel Hill, USA. 2 Department of Sociology, and When is a really small number, the above mixture normal distribution is approximately a mixture distribution of a normal distribution plus a point mass at zero. Secondly, rather than drawing from the posterior distribution of all the random effects b as a vector, we modify the algorithm to draw bj component wise conditional on the indicator Ij. Specifically, if Ij = 1, bj is drawn from the marginal conditional distribution Wang et al. Saritas-Yildirim et al. BMC Genomics 16:380 DOI 10.1186/s12864-015-1591-4 RESEARCH ARTICLE Open Dihydroartemisinin Access Identification of REST targets in the Xenopus tropicalis genome Banu Saritas-Yildirim1, Christopher P Childers1,2, Christine G Elsik1,2,3 and Elena M Silva1 Abstract Background: A major role of REST is to inhibit the expression of neuronal genes in neural stem cells and non-neuronal cells by binding to a 21 bp consensus sequence and recruiting epigenetic and regulatory cofactors to gene regulatory regions. In neural stem cells, REST silences differentiation-promoting genes to prevent their premature expression and is central to the regulation of neurogenesis and the balance of neural stem cells and neurons. Results: To understand the role of REST in vertebrate neurogenesis, we performed a genome-wide screen for REST targets in Xenopus tropicalis. We identified 742 neuron-restrictive silencer elements associated with 1396 genes that are enriched in neuronal function. Comparative analyses revealed that characteristics of NRSE motifs in frog are similar to those in mammals in terms of the distance to target genes, frequency of motifs and the repertoire of putative target genes. In addition, we identified four F-box ubiquitin ligases as putative REST targets and determined that they are expressed in neuronal tissues during Xenopus development. Conclusion: We identified a PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19801147 conserved core of putative target genes in human, mouse and frog that may be fundamental to REST function in vertebrates. We demonstrate that NRSE sites are associated with both protein-coding genes and lncRNAs in the human genome. Furthermore, we demonstrate that REST binding sites are abundant in low gene-occupancy regions of the human genome but this is not due to an increased association with non-coding RNAs. Our findings identify novel targets of REST and broaden the known mechanism of REST-mediated silencing in neurogenesis. Keywords: REST, NRSE, Xenopus, Genome-wide screen, Neurogenesis, Gene silencing Background The repressor element-1 silencing transcription factor silences neuronal genes in non-neuronal tissues and in neural stem cells of vertebrates to restrict their expression to neurons and to prevent premature differentiation, respectively. REST binds to a conserved 21-bp neuron-restrictive silencing element in the flanking regulatory regions or introns of many neuronal genes and recruits the cofactors CoREST and Sin3A to form repressor complexes with histone deactylases, histone modifying proteins, the methyl-CpG-binding protein MeCP and components of the SWI-SNF chromatin remodeling complexes. Together these Correspondence: [email protected] 1 Department of Biology, Georgetown University, 411 Regents Hall, Washington, DC 20057, USA Full list of author information is available at the end of the article proteins change the architecture of DNA to heterochromatin and silence target genes. REST is critical for
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