SeRNA PAM-1 interacts with Ddx5 to regulate skeletal muscle satellite cell activation and aging through trans regulation of Timp2 expression [PAM-1 KO ChIP-seq]

ABSTRACT: There is an absolute requirement of Pax7 for the normal function of MuSCs during regenerative myogenesis in skeletal muscle at any stage of life. Here using RNA-seq, H3K27ac and Pax7 ChIP-seq, we discover PAM-1 (Pax7 Associated Muscle lncRNA) that is enriched in activated skeletal muscle satellite cells (ASCs) 24 and 48 hours after activation. Knockdown of PAM-1 reduces proliferating Pax7+Myod+ ASCs number, while overexpression of PAM-1 increases ASCs number. Mechanistically, PAM-1 is located on ASCs and myoblast specific super-enhancer (SE), and we categorize it as seRNA. Through a series of multiomics analysis of PAM-1 interactome in myoblast including PAM-1-DNA interaction by ChIRP-seq, PAM-1 SE-DNA interaction by 4C-seq, PAM-1-protein interaction by mass spectrometry and ChIP-seq, we identify a novel class of transcriptional regulation that seRNA PAM-1 interacts with RNA binding protein Ddx5 and tethers PAM-1 SE to regulate inter-chromosomal targets Timp2. Altogether, our findings identify PAM-1 is driven by Pax7 in ASC and myoblast to regulate myogenic activation through binding with Ddx5 and targeting Timp2.

ORGANISM(S): Mus musculus

PROVIDER: GSE180069 | GEO | 2022/07/12

REPOSITORIES: GEO