title: Autonomous actions of the human growth hormone long-range enhancer.
abstract: The human growth hormone (hGH) gene is controlled by a long-range enhancer, HSI, located 14.5 kb 5' to the hGH promoter. HSI establishes a domain of noncoding transcription that is 'looped' to the hGH promoter as an essential step in initiating hGH gene expression. Thus, defining how HSI generates its domain of noncoding transcription is central to understanding its long-range function. Here, we demonstrate that activation of noncoding transcription reflects an HSI-autonomous activity fully independent of interactions with linked gene promoters and occurring in spatial and temporal synchrony with initiation of GH expression in the embryonic pituitary. HSI establishes its noncoding transcription start sites (TSS) over a defined distance from its core determinants and in a manner independent of local primary sequences. The interval between HSI and it TSS co-maps with a domain of disordered and/or highly mobile nucleosomes specific to the pituitary locus. Thus, a localized chromatin reconfiguration by HSI and consequent establishment of an adjacent domain of noncoding transcription constitute initiating events in long-range enhancer function within the hGH locus.
authors: Department of Genetics, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Eung Jae
authors: EJ
authors: Yoo
authors: Department of Genetics, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Christopher D
authors: CD
authors: Brown
authors: Department of Genetics, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Yu-Cheng
authors: YC
authors: Tsai
authors: Department of Genetics, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA Department of Medicine, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Nancy E
authors: NE
authors: Cooke
authors: Department of Genetics, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA Department of Medicine, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA liebhabe@mail.med.upenn.edu.
authors: Stephen A
authors: SA
authors: Liebhaber
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry; D004742:Enhancer Elements, Genetic; D019382:Human Growth Hormone / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000196:embryology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D022661:RNA, Untranslated / Q000096:biosynthesis; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D022661:RNA, Untranslated; D019382:Human Growth Hormone