title: Tissue-specific chromatin modifications at a multigene locus generate asymmetric transcriptional interactions.
abstract: Random assortment within mammalian genomes juxtaposes genes with distinct expression profiles. This organization, along with the prevalence of long-range regulatory controls, generates a potential for aberrant transcriptional interactions. The human CD79b/GH locus contains six tightly linked genes with three mutually exclusive tissue specificities and interdigitated control elements. One consequence of this compact organization is that the pituitary cell-specific transcriptional events that activate hGH-N also trigger ectopic activation of CD79b. However, the B-cell-specific events that activate CD79b do not trigger reciprocal activation of hGH-N. Here we utilized DNase I hypersensitive site mapping, chromatin immunoprecipitation, and transgenic models to explore the basis for this asymmetric relationship. The results reveal tissue-specific patterns of chromatin structures and transcriptional controls at the CD79b/GH locus in B cells distinct from those in the pituitary gland and placenta. These three unique transcriptional environments suggest a set of corresponding gene expression pathways and transcriptional interactions that are likely to be found juxtaposed at multiple sites within the eukaryotic genome.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Blvd., 428 Clinical Research Building, Philadelphia, PA 19104, USA.
authors.forename: Eung Jae
authors.initials: EJ
authors.lastname: Yoo
authors.forename: Isabela
authors.initials: I
authors.lastname: Cajiao
authors.forename: Jeong-Seon
authors.initials: JS
authors.lastname: Kim
authors.forename: Atsushi P
authors.initials: AP
authors.lastname: Kimura
authors.forename: Aiwen
authors.initials: A
authors.lastname: Zhang
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Cooke
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Liebhaber
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D051925:CD79 Antigens / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D014158:Transcription, Genetic
chemical_list: D051925:CD79 Antigens; C497883:CD79B protein, human; D002843:Chromatin; D006657:Histones; D019382:Human Growth Hormone; D003850:Deoxyribonuclease I