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Bystander gene activation by a locus control region.
Isabela Cajiao1, Aiwen Zhang, Eung Jae Yoo
1Departments of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
The EMBO Journal
|September 11, 2004
Summary
A B-cell specific gene, Igbeta, is unexpectedly transcribed in the pituitary gland. This bystander gene activation is driven by the human growth hormone locus control region, challenging current models of tissue-specific gene regulation.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- Mammalian genomes exhibit potential for gene interference due to gene proximity and long-range transcriptional controls.
- The Igbeta (CD79b) gene, typically B-cell specific, is located near the pituitary-specific human growth hormone (hGH) gene and its locus control region (hGH LCR).
Purpose of the Study:
- To investigate the unexpected high-level transcription of the Igbeta gene in the pituitary gland.
- To elucidate the regulatory mechanisms underlying this aberrant gene expression and its dependence on the hGH LCR.
Main Methods:
- Analysis of gene expression in human pituitary and B cells.
- Investigation of epigenetic modifications associated with the hGH LCR.
- Functional studies to assess the role of the hGH LCR in Igbeta transcription.
Main Results:
- High-level transcription of the human Igbeta gene was detected in the pituitary gland.
- Pituitary Igbeta transcription was found to be dependent on epigenetic modifications regulated by the hGH LCR.
- Igbeta expression in B cells remained independent of hGH LCR activity.
Conclusions:
- Fortuitous gene positioning within an active chromatin domain can lead to robust 'bystander' gene activation in unrelated tissues.
- This finding challenges established concepts of tissue specificity and models of active chromatin domains.
- Gene regulation can be influenced by the genomic neighborhood and epigenetic landscape beyond the gene's intrinsic regulatory elements.