Minimal in vivo requirements for developmentally regulated cardiac long intergenic non-coding RNAs.
Matthew R GeorgeQiming DuanAbigail NagleIrfan S KathiriyaYu HuangKavitha RaoSaptarsi M HaldarBenoit G BruneauPublished in: Development (Cambridge, England) (2019)
Long intergenic non-coding RNAs (lincRNAs) have been implicated in gene regulation, but their requirement for development needs empirical interrogation. We computationally identified nine murine lincRNAs that have developmentally regulated transcriptional and epigenomic profiles specific to early heart differentiation. Six of the nine lincRNAs had in vivo expression patterns supporting a potential function in heart development, including a transcript downstream of the cardiac transcription factor Hand2, which we named Handlr (Hand2-associated lincRNA), Rubie and Atcayos We genetically ablated these six lincRNAs in mouse, which suggested genomic regulatory roles for four of the cohort. However, none of the lincRNA deletions led to severe cardiac phenotypes. Thus, we stressed the hearts of adult Handlr and Atcayos mutant mice by transverse aortic banding and found that absence of these lincRNAs did not affect cardiac hypertrophy or left ventricular function post-stress. Our results support roles for lincRNA transcripts and/or transcription in the regulation of topologically associated genes. However, the individual importance of developmentally specific lincRNAs is yet to be established. Their status as either gene-like entities or epigenetic components of the nucleus should be further considered.
Keyphrases
- transcription factor
- left ventricular
- genome wide identification
- heart failure
- dna binding
- hypertrophic cardiomyopathy
- cardiac resynchronization therapy
- acute myocardial infarction
- copy number
- gene expression
- mitral valve
- poor prognosis
- atrial fibrillation
- dna methylation
- aortic valve
- oxidative stress
- risk assessment
- climate change
- type diabetes
- coronary artery disease
- human health
- long non coding rna
- stress induced
- pulmonary artery
- skeletal muscle
- wild type
- high fat diet induced
- heat shock
- childhood cancer
- transcatheter aortic valve replacement
- single cell
- percutaneous coronary intervention