EZH2 Dynamically Associates With Non-coding RNAs in Mouse Hearts After Acute Angiotensin II Treatment
Open Access
- 25 February 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cardiovascular Medicine
Abstract
Enhancer of zeste 2 (EZH2) governs gene reprogramming during cardiac hypertrophy through epigenetic remodeling, a process regulated by numerous non-coding RNAs (ncRNAs). However, the dynamic interaction between EZH2 and ncRNAs upon hypertrophic stimulation remains elusive. Here we performed an unbiased profiling for EZH2-associated ncRNAs in mouse hearts treated with Angiotensin II (AngII) at different time points (0, 4, and 24 h). The interactions between EZH2 and long ncRNAs (lncRNAs), Chaer, Mirt1, Hotair, and H19, were validated by PCR. RIP-seq analysis identified a total of 126 ncRNAs to be significantly associated with EZH2. These ncRNAs covers all five categories including intergenic, antisense, intron-related, promoter-related and both antisense and promoter-related. According to their changing patterns after AngII treatment, these ncRNAs were clustered into four groups, constantly enhanced, transiently enhanced, constantly suppressed and transiently suppressed. Structural prediction showed that EZH2 bound to hairpin motifs in ncRNAs including snoRNAs. Interaction strength prediction and RNA pull-down assay confirmed the direct interaction between EZH2 and Snora33. Interestingly, two antisense lncRNAs of Malat1, Gm20417, and Gm37376, displayed different binding patterns from their host gene after AngII treatment, suggesting a crucial role of this genomic locus in modulating EZH2 behavior. Our findings reveal the profile of EZH2-associated ncRNAs upon hypertrophic stimulation, and imply a dynamic regulation of EZH2 function in cardiac hypertrophy.Funding Information
- National Natural Science Foundation of China (81722007, 82070231)
- National Health and Family Planning Commission of the People's Republic of China (2017ZX10304402001-008)
This publication has 58 references indexed in Scilit:
- Molecular Mechanisms Directing PRC2 Recruitment and H3K27 MethylationMolecular Cell, 2019
- A Compound AC1Q3QWB Selectively Disrupts HOTAIR-Mediated Recruitment of PRC2 and Enhances Cancer Therapy of DZNepTheranostics, 2019
- Long non-coding RNA: its evolutionary relics and biological implications in mammals: a reviewJournal of Animal Science and Technology, 2018
- Interactions between microRNAs and long non-coding RNAs in cardiac development and repairPharmacological Research, 2018
- Non-coding RNA networks in cancerNature Reviews Cancer, 2017
- Non-coding RNAs as drug targetsNature Reviews Drug Discovery, 2016
- Long noncoding RNAs in cardiac development and ageingNature Reviews Cardiology, 2015
- Landscape of transcription in human cellsNature, 2012
- Long Noncoding RNA as Modular Scaffold of Histone Modification ComplexesScience, 2010
- Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expressionProceedings of the National Academy of Sciences of the United States of America, 2009