title: An RNA-independent linkage of noncoding transcription to long-range enhancer function.
abstract: The detection of noncoding transcription at multiple enhancers within the mammalian genome raises critical questions regarding whether and how this activity contributes to enhancer function. Here, using in vivo analysis of a human growth hormone (hGH) transgene locus, we report that activation of a domain of noncoding transcription adjacent to the long-range hGH-N enhancer, HSI, is established by the enhancer independent of any interactions with its target promoter. We further demonstrate that the appearance of this enhancer-linked noncoding transcription is temporally and spatially concordant with induction of hGH-N in the embryonic pituitary. Finally, we show that the level of transcriptional enhancement of hGH-N by HSI is directly related to the intensity of HSI-dependent noncoding transcription and is fully independent of the structure of the locally transcribed RNA. These data extend our understanding of the relationship of long-range enhancer activity to enhancer-dependent noncoding transcription and establish a model that may be of general relevance to additional mammalian loci.
authors.affiliation: Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Eung Jae
authors.initials: EJ
authors.lastname: Yoo
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Cooke
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Liebhaber
mesh_terms: D000818:Animals; D004742:Enhancer Elements, Genetic; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D009865:Oocytes / Q000378:metabolism; D010902:Pituitary Gland / Q000196:embryology / Q000378:metabolism; D012313:RNA / Q000235:genetics; D015533:Transcriptional Activation; D019076:Transgenes
chemical_list: D019382:Human Growth Hormone; D012313:RNA