Heart failure & cardiomyopathies
A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network
Authors' conclusion
Transcriptional changes in the atria observed in human HF directly antagonize the atrial rhythm gene regulatory network, providing a genomic link between HF and AF risk independent of atrial remodeling.
Study context
- Population
- Human atria in heart failure (HF); mice with adult cardiomyocyte-specific FOG2 overexpression
Methodological detailshuman atrial tissue, mouse model
- Human atrial tissue
- Mouse model
Main finding
As reported in the abstract
- FOG2 significantly upregulated in human atria during HF
- Adult cardiomyocyte-specific FOG2 overexpression in mice caused primary spontaneous atrial fibrillation (AF) before development of HF or atrial remodeling
- FOG2 overexpression generated arrhythmia substrate and trigger in cardiomyocytes, incl. calcium cycling defects
- FOG2 repressed atrial gene expression promoted by TBX5
- FOG2 bound a subset of GATA4/TBX5 co-bound genomic locations, defining a shared atrial gene regulatory network
- FOG2 repressed TBX5-dependent transcription from a subset of co-bound enhancers, incl. a conserved enhancer at the Atp2a2 locus
- Atrial rhythm abnormalities from Tbx5 haploinsufficiency rescued by Zfpm2 haploinsufficiency
Original publication
A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network. Circulation. Published 8 January 2024. doi:10.
Summarised from the published abstract; every number is checked against it