Abstract
Several long non-coding RNAs (lncRNAs) have been reported regulate the expression of neighbor protein-coding genes at post-transcriptional, transcriptional and epigenetic levels. Dmp1 (Dentin matrix protein 1), encoding a non-collagenous extracellular matrix protein, plays an important role in dentin and bone mineralization. However, the transcriptional regulation of lncRNA on Dmp1 has not been reported. In this study, we identified a novel lncRNA named lnc-DMP1, which is near the Dmp1 gene region and undergoes remarkable changes during mandible development. lnc-DMP1 is co-localized and significantly expressed correlation with Dmp1 in embryonic and postnatal mouse mandibles. In MC3T3-E1 cells, lnc-DMP1 positively regulates DMP1 expression and skeletal mineralization. Furthermore, lnc-DMP1 induces the promoter activity of Dmp1 by modulating H3K27Ac enrichment in the Dmp1 promoter. In conclusion, our results indicate that lnc-DMP1 is a novel lncRNA near the Dmp1 gene region and regulates Dmp1 expression by modulating the H3K27 acetylation level of Dmp1 promoter.
Highlights
Long non-coding RNAs are defined as a subgroup of non-coding RNA molecules that consist of at least 200 nucleotides and exhibit no or limited protein-coding capability (Roberts et al, 2014; Marchese et al, 2017)
Through stringent classification (| log2 fold change (E18D/postnatal 2-week-old (P2W)) | >4, false discovery rate (FDR) < 0.001), 808 and 408 long non-coding RNAs (lncRNAs) were found to be up-regulated (log2 fold change (E18D/P2W) >4) and downregulated (log2 fold change (E18D/P2W) < −4) (Figure 1B), respectively. These results suggested that lncRNAs might be involved in the regulation of mouse mandible development
To investigate lncRNAs that might modulate the transcriptional expression of Dmp1 in cis, we searched lncRNAs located within 100 kb of the Dmp1 gene region (Chromosome 5:104202613104214102) from the lncRNA-seq data
Summary
Long non-coding RNAs (lncRNAs) are defined as a subgroup of non-coding RNA molecules that consist of at least 200 nucleotides and exhibit no or limited protein-coding capability (Roberts et al, 2014; Marchese et al, 2017). Since the major role of Xist in X-chromosome inactivation was first described (Brockdorff et al, 1992; Brown et al, 1992), studies have demonstrated that lncRNAs function in multiple cellular processes, such as genomic locus imprinting (Kanduri, 2016), antiviral response (Fortes and Morris, 2016) and differentiation and development (Fatica and Bozzoni, 2014). Studies have investigated various mechanisms underlying lncRNA functions. Some nuclear lncRNAs are expressed from imprinted loci function as molecular scaffolds that recruit chromatin-modifying complexes and regulate gene expression in cis by altering the chromatin structures of target genes (Lee and Bartolomei, 2013; Melo et al, 2013). Other lncRNAs modulate gene expression in trans by interfering with transcriptional machineries or maintaining the structures of nuclear speckles (Prasanth et al, 2005; Clemson et al, 2009; Sunwoo et al, 2009). Some cytosolic lncRNAs have been suggested to regulate mRNA splicing, mRNA decay, protein translation and protein stability (Yoon et al, 2013; Quinn and Chang, 2016)
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