Tissue-specific chromatin modifications at a multigene locus generate asymmetric transcriptional interactions.
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.
Yoo
Eung Jae
EJ
Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Blvd., 428 Clinical Research Building, Philadelphia, PA 19104, USA.
Cajiao
Isabela
I
Kim
Jeong-Seon
JS
Kimura
Atsushi P
AP
Zhang
Aiwen
A
Cooke
Nancy E
NE
Liebhaber
Stephen A
SA
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
D051925:CD79 Antigens; C497883:CD79B protein, human; D002843:Chromatin; D006657:Histones; D019382:Human Growth Hormone; D003850:Deoxyribonuclease I