title: Locus control region transcription plays an active role in long-range gene activation.
abstract: Activation of eukaryotic genes often relies on remote chromatin determinants. How these determinants function remains poorly understood. The hGH gene is activated by a 5'-remote locus control region (LCR). Pituitary-specific DNase I hypersensitive site I (HSI), the dominant hGH LCR element, is separated from the hGH-N promoter by a 14.5 kb span that encompasses the B-lymphocyte-specific CD79b gene. Here, we describe a domain of noncoding Pol II transcription in pituitary somatotropes that includes the hGH LCR and adjacent CD79b locus. This entire "LCR domain of transcription" is HSI [corrected] dependent and terminates 3' to CD79b, leaving a gap in transcription between this domain and the target hGH-N promoter. Insertion of a Pol II terminator within the LCR blocks CD79b transcription and represses hGH-N expression. These data document an essential role for LCR transcription in long-range control, link "bystander"CD79b transcription to this process, and support a unique model for locus activation.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Yugong
authors.initials: Y
authors.lastname: Ho
authors.forename: Felice
authors.initials: F
authors.lastname: Elefant
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Liebhaber
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Cooke
mesh_terms: D000107:Acetylation; D000818:Animals; D051925:CD79 Antigens / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015723:Gene Library; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics; D006657:Histones / Q000378:metabolism; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D019901:Locus Control Region / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D010902:Pituitary Gland / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013728:Terminator Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D051925:CD79 Antigens; D006657:Histones; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D012319:RNA Polymerase II