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.

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

“…[18][19][20] It has been reported that HOTAIR regulates gene expression via epigenetic modifications. 21 For example, Rinn et al demonstrated that HOTAIR interacts with polycomb-repressive complex 2 (PRC2) to increase the trimethylation of histone H3 lysine-27 (H3K27), resulting in the reduction of HOXD gene expression. 21 However, the role of HOTAIR in liver fibrosis has never been studied.…”

LncRNA HOTAIR/miR‐613/c‐met axis modulated epithelial‐mesenchymal transition of retinoblastoma cells

“…Alternatively, lncRNA H19 inhibited progression of retinoblastoma cells via offsetting the action of miR‐17‐92 cluster,41 and lncRNA CCAT1 negatively regulated miR‐218‐5p to facilitate the proliferation and growth of SO‐RB50 and Y79 cell lines 13. HOTAIR, situated in chromosome 12 between HOXC11 and HOXC12, covered a length of 2.2 nt,14, 42 so it was also called as long intergenic non‐coding RNA (lincRNA). The lncRNA was equipped with 2 active domains, including 5′‐end that could recruit PRC2, and 3′‐end that combined with lysine specific demethylase (LSD1), RE1‐silencing transcription factor (REST) and REST co‐inhibitory protein (CoREST) 43.…”

New meaning in the message: Noncoding RNAs and their role in retinal development

“…HOTAIR is an OST located at the boundary of two chromatin domains at the HOXC locus (Rinn et al, 2007). Depletion of HOTAIR had no effect on transcription of genes in the HOXC cluster, but did lead to transcriptional activation at the HOXD cluster, which lies on a separate chromosome.…”