Bystander gene activation by a locus control region
| Autor: | Stephen A. Liebhaber, Isabela Cajiao, Nancy E. Cooke, Eung Jae Yoo, Aiwen Zhang |
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| Rok vydání: | 2004 |
| Předmět: |
Adenoma
Transcriptional Activation Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Article Mice Transcription (biology) Antigens CD Animals Humans Tissue Distribution Epigenetics Molecular Biology Gene Locus control region Cells Cultured Regulation of gene expression Genetics B-Lymphocytes General Immunology and Microbiology Human Growth Hormone General Neuroscience CD79B Locus Control Region Chromatin Mice Inbred C57BL Gene Expression Regulation Organ Specificity Pituitary Gland Human genome CD79 Antigens |
| Zdroj: | The EMBO journal. 23(19) |
| ISSN: | 0261-4189 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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