Bystander gene activation by a locus control region.
Random assortment of genes within mammalian genomes establishes the potential for interference between neighboring genes with distinct transcriptional specificities. Long-range transcriptional controls further increase this potential. Exploring this problem is of fundamental importance to understanding gene regulation. In the human genome, the Igbeta (CD79b) gene is situated between the pituitary-specific human growth hormone (hGH) gene and its locus control region (hGH LCR). Igbeta protein is considered B-cell specific; its only known role is in B-cell receptor signaling. Unexpectedly, we found that hIgbeta is transcribed at high levels in the pituitary. This Igbeta transcription is dependent on pituitary-specific epigenetic modifications generated by the hGH LCR. In contrast, expression of Igbeta at its native site in B cells is independent of hGH LCR activity. These studies demonstrated that a gene with tissue-restricted transcriptional determinants (B cell) can be robustly activated in an unrelated tissue (pituitary) due to fortuitous positioning within an active chromatin domain. This 'bystander' gene activation pathway impacts on current concepts of tissue specificity and models of active chromatin domains.
Cajiao
Isabela
I
Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Zhang
Aiwen
A
Yoo
Eung Jae
EJ
Cooke
Nancy E
NE
Liebhaber
Stephen A
SA
D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D051925:CD79 Antigens; D002478:Cells, Cultured; D002843:Chromatin / Q000502:physiology*; D005786:Gene Expression Regulation; D019382:Human Growth Hormone / Q000502:physiology*; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity; D010902:Pituitary Gland / Q000378:metabolism*; D014018:Tissue Distribution; D015533:Transcriptional Activation
D015703:Antigens, CD; D051925:CD79 Antigens; C497883:CD79B protein, human; C497884:Cd79b protein, mouse; D002843:Chromatin; D019382:Human Growth Hormone