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Long Non-Coding RNA Modulation of VEGF-A during Hypoxia
Tiina Nieminen1,2, Tristan A Scott3, Feng-Mao Lin4
1The Center for Gene Therapy, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA. timaniem@gmail.com.
Non-Coding RNA
|November 23, 2018
Summary
Two long non-coding RNAs (lncRNAs) regulate vascular endothelial growth factor A (VEGF-A) gene expression. These antisense lncRNAs act as enhancer-like elements at the VEGF-A promoter during hypoxia.
Area of Science:
- Molecular Biology
- Gene Regulation
- RNA Biology
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in gene expression modulation.
- Vascular endothelial growth factor A (VEGF-A) is crucial for blood vessel formation and a therapeutic target for ischemic diseases.
Purpose of the Study:
- To investigate the functional role of two antisense VEGF-A lncRNAs, RP1-261G23.7 and EST AV731492, in regulating VEGF-A transcription under hypoxic conditions.
Main Methods:
- Analysis of lncRNA polyadenylation status.
- Quantitative assessment of lncRNA and VEGF-A expression during hypoxia.
- Chromatin immunoprecipitation to determine lncRNA localization at the VEGF-A promoter and upstream regions.
- Assay for enhancer marks (H3K27ac, H3K9ac) associated with lncRNA binding sites.
Main Results:
- Both RP1-261G23.7 and EST AV731492 lncRNAs are polyadenylated and upregulated with VEGF-A during hypoxia.
- These lncRNAs localize to the VEGF-A promoter and upstream elements in a hypoxia-dependent manner.
- The lncRNAs associate with enhancer marks H3K27ac and H3K9ac, suggesting a role in transcriptional activation.
Conclusions:
- Antisense VEGF-A lncRNAs RP1-261G23.7 and EST AV731492 function as promoter enhancer-like elements.
- These lncRNAs may act as scaffolds for protein and small RNA complexes at the VEGF-A promoter.
- This mechanism provides novel insights into VEGF-A transcriptional regulation in response to hypoxia.
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