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| Status |
Public on Sep 28, 2023 |
| Title |
Disrupted propionate metabolism evokes transcriptional changes in the heart by increasing histone acetylation and propionylation [RNA-Seq 2] |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Propiogenic substrate catabolism and gut bacteria produce propionate, a post-translational protein modifier. Here, using a mouse model of propionic acidaemia (PA), we characterise how disturbances to propionate metabolism modify histones and affect cardiac gene expression and function. Plasma propionate was raised in PA mice, but male hearts accumulated a smaller propionyl-CoA excess, correlating with -alanine build-up. Raising -alanine experimentally in myocytes cultured under propionate-stress reduced propionyl-CoA and partially reversed the propionate-evoked metabolic disturbance. Female PA hearts manifested a moderate diastolic dysfunction phenotype, with raised diastolic [Ca2+], expanded end-systolic ventricular volume, and reduced stroke volume. Differentially-expressed genes included Pde9a and Mme that relate to contractile dysfunction through down-scaled cGMP signalling, consistent with phosphoproteome changes. Propionate was traced to histone H3 propionylation and increased acetylation genome-wide, including at Pde9a and Mme promoters, with more pronounced effects in female PA hearts. We link perturbed propionate metabolism to epigenetic changes that impact cardiac function.
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| Overall design |
RNA-seq
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| |
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| Contributor(s) |
Park KC, Crump NT, Milne TA, Swietach P |
| Citation(s) |
38500966 |
| |
| Submission date |
Jun 10, 2022 |
| Last update date |
Apr 02, 2024 |
| Contact name |
Pawel Swietach |
| Organization name |
University of Oxford
|
| Department |
Department of Physiology, Anatomy & Genetics
|
| Street address |
Sherrington Building, Parks Road
|
| City |
Oxford |
| ZIP/Postal code |
OX1 3PT |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL25947 |
Illumina NovaSeq 6000 (Rattus norvegicus) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE205838 |
Disrupted propionate metabolism evokes transcriptional changes in the heart by increasing histone acetylation and propionylation |
|
| Relations |
| BioProject |
PRJNA847925 |
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