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BMC Genomics

, 16:380

First Online: 14 May 2015Received: 15 May 2014Accepted: 28 April 2015DOI: 10.1186-s12864-015-1591-4

Cite this article as: Saritas-Yildirim, B., Childers, C.P., Elsik, C.G. et al. BMC Genomics 2015 16: 380. doi:10.1186-s12864-015-1591-4

Abstract

BackgroundA major role of REST repressor element-1 silencing transcription factor 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.

ResultsTo 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 NRSE 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.

ConclusionWe identified a 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.

KeywordsREST NRSE Xenopus Genome-wide screen Neurogenesis Gene silencing AbbreviationsRESTRepressor element 1 silencing transcription factor

NRSENeuron-restrictive silencing element

ncRNANon-coding RNA

lncRNALong-non coding RNA

miRNAMicroRNA

rRNARibosomal RNA

snRNASmall nuclear RNA

snoRNASmall nucleolar RNA

MeCPMethyl-CpG-binding protein

βTRCBeta-transducin repeat containing protein

FbxwF-box protein with WD40 domain

FbxlF-box protein with leucine rich repeat

FbxoF-box protein with domain other than WD40 or leucine rich repeat

BAF53aBrg-Brm associated factor 53a

hESCHuman embryonic stem cell

GDGene-distant regions

GOGene ontology

WISHWhole-mount in situ hybridization

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-015-1591-4 contains supplementary material, which is available to authorized users.

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Autor: Banu Saritas-Yildirim - Christopher P Childers - Christine G Elsik - Elena M Silva

Fuente: https://link.springer.com/







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