dissecting the transcriptional regulatory properties of human chromosome 16 highly conserved non-coding regions解剖人类染色体16的转录监管性质高度保守的非编码区域.pdfVIP

Dissecting the Transcriptional Regulatory Properties of Human Chromosome 16 Highly Conserved Non-Coding Regions ´ 1 1 1 ´ 1 2 Jose Luis Royo , Carmen Hidalgo , Yolanda Roncero , Marıa Angeles Seda , Altuna Akalin , Boris 2,3 1 ´ ´ 1 Lenhard , Fernando Casares , Jose Luis Gomez-Skarmeta * ´ 1 Centro Andaluz de Biologia del Desarrollo, CSIC-Universidad Pablo de Olavide-Junta de Andalucıa, Sevilla, Spain, 2 Computational Biology Unit, Bergen Center for Computational Science, University of Bergen, Bergen, Norway, 3 Sars Centre for Marine Molecular Biology, University of Bergen, Bergen, Norway 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.