Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs

John L. Rinn, Michael Kertesz, Jordon K. Wang, Sharon L. Squazzo, Xiao Xu, Samantha A. Brugmann, L. Henry Goodnough, Jill A. Helms, Peggy J. Farnham, Eran Segal, Howard Y. Chang

Research output: Contribution to journalArticle

2762 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1311-1323
Number of pages13
JournalCell
Volume129
Issue number7
DOIs
StatePublished - Jun 29 2007

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    Rinn, J. L., Kertesz, M., Wang, J. K., Squazzo, S. L., Xu, X., Brugmann, S. A., Goodnough, L. H., Helms, J. A., Farnham, P. J., Segal, E., & Chang, H. Y. (2007). Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs. Cell, 129(7), 1311-1323. https://doi.org/10.1016/j.cell.2007.05.022