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Single-cell RNA-sequencing reveals the role of p300/CBP in calcium handing ability of prepubertal RV cardiomyocytes.

ABSTRACT: The expression of genes is determined by the openness and accessibility of chromatin, which is the most basic phenomenon in the field of life sciences.The histone acetylase p300/CBP (CBP and P300 have similar structures and functions) can catalyze the acetylation of the lysine at the 27th position of histone H3(H3K27ac), which changes the the openness and accessibility of chromatin. Thus, p300/CBP are considered to be two of the most important transcription co-factors. To further understanding the role of p300/CBP in regulating calcium handing of prepubertal RV CMs, we first detected its expression in the prepubertal RV.The expressions of p300/CBP in the prepubertal dysfunctional RV were significantly downregulated, consistent with the data of p300-ChIP-seq, which showing the loss of p300 chromatin occupancy in calcium handing genes. Then we knocked out p300/CBP in neonatal mouse. p300/CBP knockout cardiomyocytes showed a impaired calcium handing ability, similar to that in prepubertal dysfunctional RV cardiomyocytes. These results confirmed the role of p300 in regulating the calcium handing ability of prepubertal RV CMs.

ORGANISM(S): Mus musculus

PROVIDER: GSE242193 | GEO | 2024/08/16

REPOSITORIES: GEO

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Project description:Background: Right ventricular (RV) and left ventricular (LV) myocardium differ in their response to pressure-overload hypertrophy (POH). In this report we use microarray and proteomic analyses to identify pathways modulated by LV-, and RV-POH in the immature heart. Methods: Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta (LV-POH; n=6). RV-POH was achieved by banding the pulmonary artery (n=6). Sham–control animals (SC; n=6 each) were sham-manipulated. Following 4 (LV-POH) and 6 weeks (RV-POH) recovery, the hearts were removed and matched sample RNA and proteins were isolated for microarray and proteomic analysis. Results: There was no difference in body weight in RV-, LV-POH vs. SC but there was a significant increase vs. SC in RV (3.2±0.8g vs. 1.2±0.3g; P<0.01) and LV weight (7.08±0.6g vs. 4.02±0.2g; P<0.01). Fractional area change (RV-POH) and shortening fraction (LV-POH) decreased significantly (23±6 vs. 47±6 and 21±4 vs.44±2, respectively, P<0.01). Microarray analysis demonstrated that LV-POH enriched pathways for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium and protein kinase-A signalling. RV-POH enriched pathways for cardiac oxidative phosphorylation. Proteomic analysis revealed 19 proteins were uniquely expressed in LV-POH vs. SC. Functional annotation clustering analysis indicated significant enrichment for the mitochondrion, cellular macromolecular complex assembly and oxidative phosphorylation. RV-POH had 15 uniquely expressed proteins vs. SC. Functional annotation clustering analysis indicated significant enrichment in structural constituents of muscle, cardiac muscle tissue development and calcium handling. Conclusion: Our results identify unique transcript and protein expression profiles in LV, RV-POH and provide new insight into the biological basis of ventricular specific hypertrophy. 3 different conditions: PAB-RV vs. Sham-control RV, PAB-RV [test] vs. PAB-LV [control], AOB-LV vs. Sham-control LV.

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Single-cell RNA-sequencing reveals the role of p300/CBP in calcium handing ability of prepubertal RV cardiomyocytes.

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