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


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.

SUBMITTER: Rinn JL 

PROVIDER: S-EPMC2084369 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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

Rinn John L JL   Kertesz Michael M   Wang Jordon K JK   Squazzo Sharon L SL   Xu Xiao X   Brugmann Samantha A SA   Goodnough L Henry LH   Helms Jill A JA   Farnham Peggy J PJ   Segal Eran E   Chang Howard Y HY  

Cell 20070601 7


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 an  ...[more]

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