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Dicer-Dependent Turnover of Intergenic Transcripts from the Human ß-Globin Gene Cluster

Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom

Received 24 May 2005/ Returned for modification 2 July 2005/ Accepted 7 August 2005

The widespread occurrence of intergenic transcription in eukaryotes is increasingly evident. Intergenic transcription in the ß-globin gene cluster has been described in murine and human cells, and models for a role in gene and chromatin activation have been proposed. In this study, we analyze intergenic transcription and the chromatin state throughout the human ß-globin gene cluster and find that the data are not consistent with such activation-linked models. Thus, intergenic transcript levels correlate with neither chromatin activation nor globin gene expression. Instead, we find that intergenic transcripts of the ß-globin gene cluster are specifically upregulated in Dicer-deficient cells. This is accompanied by a shift towards more activated chromatin as indicated by changes in histone tail modifications. Our results strongly implicate RNA interference (RNAi)-related mechanisms in regulating intergenic transcription in the human ß-globin gene cluster and further suggest that RNAi-dependent chromatin silencing in vertebrates is not restricted to the centromeres.

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