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

被引:3826
作者
Rinn, John L.
Kertesz, Michael
Wang, Jordon K.
Squazzo, Sharon L.
Xu, Xiao
Brugmann, Samantha A.
Goodnough, L. Henry
Helms, Jill A.
Farnham, Peggy J.
Segal, Eran [1 ]
Chang, Howard Y.
机构
[1] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel
[2] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA
[3] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA
[4] Univ Calif Davis, Dept Pharmacol, Genome Ctr, Livermore, CA 95616 USA
关键词
D O I
10.1016/j.cell.2007.05.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1311 / 1323
页数:13
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