title: The role of the hGH locus control region in somatotrope restriction of hGH-N gene expression.
abstract: Expression of mammalian GH is normally restricted to somatotropes and somatolactotropes (somatotrope lineages) in the anterior pituitary. The basis for this restriction remains incompletely understood. Recent studies indicate that deoxyribonuclease I hypersensitive site I (HSI) of the hGH locus control region, located at -14.5 kb relative to the hGH-N promoter, acts as a potent long-range enhancer of hGH-N transcription. Here we report that HSI is also critical to somatotrope-restriction of hGH-N expression. Loss of HSI activity, either by direct inactivation of HSI or by interference with HSI-dependent downstream events, results in a relaxation of hGH-N cell-type specification with expansion of hGH-N expression to the full spectrum of Pit-1 positive pituitary cell types. These findings expand the defined roles for HSI of the hGH locus control region to include somatotrope lineage restriction as well as transcriptional enhancement of hGH-N gene expression.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA. yho@mail.med.upenn.edu
authors.forename: Yugong
authors.initials: Y
authors.lastname: Ho
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Liebhaber
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Cooke
mesh_terms: D000818:Animals; D015253:Deoxyribonucleases, Type I Site-Specific / Q000235:genetics / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation; D019382:Human Growth Hormone / Q000235:genetics* / Q000378:metabolism; D019901:Locus Control Region; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011388:Prolactin / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics* / Q000378:metabolism; D052683:Somatotrophs / Q000378:metabolism*; D037322:Thyrotropin, beta Subunit / Q000378:metabolism; D050817:Transcription Factor Pit-1 / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D037322:Thyrotropin, beta Subunit; D050817:Transcription Factor Pit-1; D019382:Human Growth Hormone; D011388:Prolactin; D015253:Deoxyribonucleases, Type I Site-Specific