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      Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs.

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          Abstract

          Noncoding RNAs (ncRNA) participate in epigenetic regulation but are poorly understood. Here we characterize the transcriptional landscape of the four human HOX loci at five base pair resolution in 11 anatomic sites and identify 231 HOX ncRNAs that extend known transcribed regions by more than 30 kilobases. HOX ncRNAs are spatially expressed along developmental axes and possess unique sequence motifs, and their expression demarcates broad chromosomal domains of differential histone methylation and RNA polymerase accessibility. We identified a 2.2 kilobase ncRNA residing in the HOXC locus, termed HOTAIR, which represses transcription in trans across 40 kilobases of the HOXD locus. HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          0092-8674
          0092-8674
          Jun 29 2007
          : 129
          : 7
          Affiliations
          [1 ] Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
          Article
          S0092-8674(07)00659-9 NIHMS26949
          10.1016/j.cell.2007.05.022
          2084369
          17604720
          0d7eaa52-61d8-4953-ae84-7000c1e57845
          History

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