title: Dicer-dependent turnover of intergenic transcripts from the human beta-globin gene cluster.
abstract: The widespread occurrence of intergenic transcription in eukaryotes is increasingly evident. Intergenic transcription in the beta-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 beta-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 beta-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 beta-globin gene cluster and further suggest that RNAi-dependent chromatin silencing in vertebrates is not restricted to the centromeres.
authors.affiliation: Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom.
authors.forename: Dirk
authors.initials: D
authors.lastname: Haussecker
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Proudfoot
mesh_terms: D002503:Centromere / Q000235:genetics; D002843:Chromatin / Q000235:genetics / Q000502:physiology; D021901:DNA, Intergenic / Q000235:genetics*; D005914:Globins / Q000235:genetics*; D006367:HeLa Cells; D006657:Histones / Q000235:genetics; D006801:Humans; D005810:Multigene Family; D034622:RNA Interference; D043244:Ribonuclease III / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D021901:DNA, Intergenic; D006657:Histones; D005914:Globins; D043244:Ribonuclease III