Dataset Information

The Long Non-coding RNA lnc-DMP1 Regulates Dmp1 Expression Through H3K27Ac Modification.

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.

SUBMITTER: Xia X

PROVIDER: S-EPMC7093497 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Long Non-coding RNA lnc-DMP1 Regulates Dmp1 Expression Through H3K27Ac Modification.

Xia Xin X Ruan Yi Y Li Boya B Yu Yansong Y Kong Xiangbo X Zhuang Peilin P Wu Hong H

Frontiers in genetics 20200318

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 ne ...[more]

PMID: 32256524

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Project description:Long non-coding RNAs (lncRNAs) are master regulators of gene expression and have recently emerged as potential innovative therapeutic targets. The deregulation of lncRNA expression patterns has been associated with age-related and noncommunicable diseases in the bone tissue, including osteoporosis and tumors. However, the specific role of lncRNAs in physiological or pathological conditions in the bone tissue still needs to be further clarified, for their exploitation as therapeutic tools. In the present study, we evaluate the potential of the lncRNA CASC2 as a regulator of osteogenic differentiation and mineralization. Results show that CASC2 expression is decreased during osteogenic differentiation of human bone marrow-derived Mesenchymal Stem/Stromal cells (hMSCs). CASC2 knockdown, using small interfering RNA against CASC2 (siCASC2), increases the expression of the late osteogenic marker Bone Sialoprotein (BSP), but does not impact ALP staining level nor the expression of early osteogenic transcripts, including RUNX2 and OPG. Although siCASC2 does not impact hMSC proliferation nor apoptosis, it promotes the mineralization of hMSC cultured under osteogenic-inducing conditions, as shown by the increase of calcium deposits. Mass spectrometry-based proteomic analysis revealed that 89 proteins are regulated by CASC2 at late osteogenic stages, including proteins associated with bone diseases or anthropometric and musculoskeletal traits. Specifically, the Cartilage Oligomeric Matrix Protein (COMP) is highly enhanced by CASC2 knockdown at late stages of osteogenic differentiation, at both transcriptional and protein level. On the other hand, inhibition of COMP impairs osteoblasts mineralization as well as the expression of BSP. The results indicate that lncRNA CASC2 regulates late osteogenic differentiation and mineralization in hMSC via COMP and BSP. In conclusion, this study suggests that targeting lncRNA CASC2 could be a potential approach for modulating bone mineralization.

Dataset Information

The Long Non-coding RNA lnc-DMP1 Regulates Dmp1 Expression Through H3K27Ac Modification.

Publications

The Long Non-coding RNA lnc-DMP1 Regulates <i>Dmp1</i> Expression Through H3K27Ac Modification.

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