The human beta-globin locus control region can silence as well as activate gene expression

Feng, Y.-Q., Warin, R., Li, T., Olivier, E., Besse, A., Lobell, A., Fu, H., Lin, C. M., Aladjem, M. I. and Bouhassira, E. E. (2005) The human beta-globin locus control region can silence as well as activate gene expression. Molecular and Cellular Biology, 25(10), pp. 3864-3874. (doi: 10.1128/MCB.25.10.3864-3874.2005)

Abstract

Using recombinase-mediated cassette exchange to test multiple transgenes at the same site of integration, we demonstrate a novel chromatin context-dependent silencer activity of the β-globin locus control region (LCR). This silencer activity requires DNase I hypersensitive sites HS2 and HS3 but not HS4. After silencing, the silenced cassettes adopt a typical closed chromatin conformation (histone H3 and H4 deacetylation, histone H3-K4 methylation, DNA methylation, and replication in late S phase). In the absence of the LCR at the same site of integration, the chromatin remains decondensed. We demonstrate that the LCR is necessary but not sufficient to trigger these chromatin changes. We also provide evidence that this novel silencing activity is caused by transcriptional interference triggered by activation of transcription in the flanking sequences by the LCR.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Olivier, Dr Emmanuel
• Authors: Feng, Y.-Q., Warin, R., Li, T., Olivier, E., Besse, A., Lobell, A., Fu, H., Lin, C. M., Aladjem, M. I., and Bouhassira, E. E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Molecular and Cellular Biology
• Publisher: American Society for Microbiology
• ISSN: 0270-7306
• ISSN (Online): 1098-5549

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