Functional demarcation of active and silent chromatin domains in human HOX loci by Noncoding RNAs
Functional demarcation of active and silent chromatin domains in human HOX loci by Noncoding RNAs
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DOI：
10.1016/j.cell.2007.05.022
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发表时间：
2007-06-29
期刊：
影响因子：
64.5
通讯作者：
Chang, Howard Y.
中科院分区：
文献类型：
--
作者：
Rinn, John L.;Kertesz, Michael;Chang, Howard Y.
非编码RNA（ncRNA）参与表观遗传调控，但人们对其了解甚少。在此，我们以5个碱基对的分辨率描述了11个解剖部位中4个人类HOX基因座的转录图谱，并鉴定出231种HOX ncRNA，它们将已知转录区域延伸了30多千碱基。HOX ncRNA沿发育轴在空间上表达，并具有独特的序列基序，它们的表达界定了差异组蛋白甲基化和RNA聚合酶可及性的广泛染色体区域。我们在HOXC基因座中鉴定出一种2.2千碱基的ncRNA，称为HOTAIR，它能反式抑制HOXD基因座40千碱基范围内的转录。HOTAIR与多梳抑制复合物2（PRC2）相互作用，并且是PRC2占据HOXD基因座以及该基因座组蛋白H3赖氨酸 - 27三甲基化所必需的。因此，ncRNA的转录可能在远处界定基因沉默的染色体区域；这些结果对发育和疾病状态下的基因调控具有广泛影响。
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.