Publications by authors named "G Dobreva"
The dynamics of three-dimensional (3D) genome organization are essential to transcriptional regulation. While enhancers regulate spatiotemporal gene expression, chromatin looping is a means for enhancer-promoter interactions yielding cell-type-specific gene expression. Further, non-canonical DNA secondary structures, such as G-quadruplexes (G4s), are related to increased gene expression.
View Article and Find Full Text PDFSignal-responsive gene expression is essential for vascular development, yet the mechanisms integrating signaling inputs with transcriptional activities are largely unknown. Here we show that RNF20, the primary E3 ubiquitin ligase for histone H2B, plays a multifaceted role in sprouting angiogenesis. RNF20 mediates RNA polymerase (Pol II) promoter-proximal pausing at genes highly paused in endothelial cells, involved in VEGFA signaling, stress response, cell cycle control and mRNA splicing.
View Article and Find Full Text PDFEndothelial derived, secreted long non-coding RNAs and aggravate cardiac remodeling.
Mol Ther Nucleic Acids
September 2024
Article Synopsis
- Pathological cardiac remodeling can lead to heart failure, and the study focused on two long non-coding RNAs (lncRNAs) that are upregulated in failing hearts.
- Overexpressing these lncRNAs in mice worsened heart dysfunction and increased hypertrophy and fibrosis in response to pressure overload.
- Knocking out these lncRNAs reduced heart damage and improved blood vessel growth but also led to sudden death in some mice, highlighting their complex role in heart failure and potential as therapeutic targets.
Cardiovascular diseases, both congenital and acquired, are the leading cause of death worldwide, associated with significant health consequences and economic burden. Due to major advances in surgical procedures, most patients with congenital heart disease (CHD) survive into adulthood but suffer from previously unrecognized long-term consequences, such as early-onset heart failure. Therefore, understanding the molecular mechanisms resulting in heart defects and the lifelong complications due to hemodynamic overload are of utmost importance.
View Article and Find Full Text PDFAims: Understanding the molecular identity of human pluripotent stem cell (hPSC)-derived cardiac progenitors and mechanisms controlling their proliferation and differentiation is valuable for developmental biology and regenerative medicine.
Methods And Results: Here, we show that chemical modulation of histone acetyl transferases (by IQ-1) and WNT (by CHIR99021) synergistically enables the transient and reversible block of directed cardiac differentiation progression on hPSCs. The resulting stabilized cardiovascular progenitors (SCPs) are characterized by ISL1pos/KI-67pos/NKX2-5neg expression.