title: Dissecting the transcriptional regulatory properties of human chromosome 16 highly conserved non-coding regions.
abstract: Non-coding DNA conservation across species has been often used as a predictor for transcriptional enhancer activity. However, only a few systematic analyses of the function of these highly conserved non-coding regions (HCNRs) have been performed. Here we use zebrafish transgenic assays to perform a systematic study of 113 HCNRs from human chromosome 16. By comparing transient and stable transgenesis, we show that the first method is highly inefficient, leading to 40% of false positives and 20% of false negatives. When analyzed in stable transgenic lines, a great majority of HCNRs were active in the central nervous system, although some of them drove expression in other organs such as the eye and the excretory system. Finally, by testing a fraction of the HCNRs lacking enhancer activity for in vivo insulator activity, we find that 20% of them may contain enhancer-blocking function. Altogether our data indicate that HCNRs may contain different types of cis-regulatory activity, including enhancer, insulators as well as other not yet discovered functions.
authors.affiliation: Centro Andaluz de Biologia del Desarrollo, CSIC-Universidad Pablo de Olavide-Junta de Andalucía, Sevilla, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Royo
authors.forename: Carmen
authors.initials: C
authors.lastname: Hidalgo
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Roncero
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Seda
authors.forename: Altuna
authors.initials: A
authors.lastname: Akalin
authors.forename: Boris
authors.initials: B
authors.lastname: Lenhard
authors.forename: Fernando
authors.initials: F
authors.lastname: Casares
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Skarmeta
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D006801:Humans; D015027:Zebrafish / Q000235:genetics
chemical_list: D004247:DNA