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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE180073 | GEO | 2022/07/12

REPOSITORIES: GEO

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seRNA PAM controls skeletal muscle satellite cell proliferation and aging through trans regulation of Timp2 expression synergistically with Ddx5.

Project description:Muscle satellite cells (SCs) are responsible for muscle homeostasis and regeneration and lncRNAs play important roles in regulating SC activities. Here, in this study, we identify PAM (Pax7 Associated Muscle lncRNA) that is induced in activated/proliferating SCs upon injury to promote SC proliferation as myoblast cells. PAM is generated from a myoblast-specific super-enhancer (SE); as a seRNA it binds with a number of target genomic loci predominantly in trans. Further studies demonstrate that it interacts with Ddx5 to tether PAM SE to its inter-chromosomal targets Timp2 and Vim to activate the gene expression. Lastly, we show that PAM expression is increased in aging SCs, which leads to enhanced inter-chromosomal interaction and target genes upregulation. Altogether, our findings identify PAM as a previously unknown lncRNA that regulates both SC proliferation and aging through its trans gene regulatory activity.

| S-EPMC9381903 | biostudies-literature

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

Project description: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.

2022-07-12 | GSE180070 | GEO

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

2022-07-12 | GSE180071 | GEO

seRNA PAM-1 interacts with Ddx5 to regulate skeletal muscle satellite cell activation and aging through trans regulation of Timp2 expression [4C-Seq]

2022-07-12 | GSE180072 | GEO

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]

2022-07-12 | GSE180069 | GEO

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

2022-07-12 | GSE180068 | GEO

seRNA PAM-1 interacts with Ddx5 to regulate skeletal muscle satellite cell activation and aging through trans regulation of Timp2 expression

Project description:seRNA PAM-1 interacts with Ddx5 to regulate skeletal muscle satellite cell activation and aging through trans regulation of Timp2 expression

| PRJNA746462 | ENA

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

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

| PRJNA746465 | ENA

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

Project description:seRNA PAM-1 interacts with Ddx5 to regulate skeletal muscle satellite cell activation and aging through trans regulation of Timp2 expression [PAM-1 ChIRP-seq]

| PRJNA746467 | ENA

seRNA PAM-1 interacts with Ddx5 to regulate skeletal muscle satellite cell activation and aging through trans regulation of Timp2 expression [4C-Seq]

Project description:seRNA PAM-1 interacts with Ddx5 to regulate skeletal muscle satellite cell activation and aging through trans regulation of Timp2 expression [4C-Seq]

| PRJNA746466 | ENA

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