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Intergenic transcription in the human beta-globin gene cluster
K E Plant1, S J Routledge, N J Proudfoot
1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Molecular and Cellular Biology
|September 5, 2001
Summary
Intergenic transcription occurs in the beta-globin gene cluster, originating from an ERV9 long terminal repeat. This transcription can be induced in non-erythroid cells, suggesting broader regulatory roles.
Area of Science:
- Genetics
- Molecular Biology
- Epigenetics
Background:
- Previous studies identified intergenic transcripts in the human beta-globin gene cluster.
- Nascent transcription analysis revealed transcripts beyond the known genic regions.
Purpose of the Study:
- To investigate the origin and regulation of intergenic transcription within the beta-globin locus control region (LCR).
- To determine the erythroid specificity and potential induction mechanisms of intergenic transcription.
Main Methods:
- Analysis of nascent transcription in the human beta-globin gene cluster.
- Utilizing transgenic mouse models with human beta-globin LCR.
- Investigating intergenic transcription induction in non-erythroid cells via transinduction, transcription factor addition, and trichostatin A treatment.
Main Results:
- Transcription into the beta-globin LCR initiates within an ERV9 endogenous retroviral long terminal repeat (LTR).
- In transgenic mice lacking the ERV9 LTR, transcription initiates upstream of the locus, potentially activated by nearby mouse promoters.
- Intergenic transcription is detected throughout the transgenic globin gene locus, irrespective of erythroid developmental stage.
- While typically erythroid-specific, intergenic transcription can be induced in non-erythroid cells.
Conclusions:
- The ERV9 LTR is a key initiation site for transcription into the beta-globin LCR.
- The LCR can influence transcription initiation from endogenous promoters in adjacent genomic regions.
- Intergenic transcription within the beta-globin cluster exhibits erythroid specificity but is amenable to induction, highlighting its dynamic regulatory potential.
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