Biology subjects

Parrello, D.

Publications and source records attributed to Parrello, D..

2 recordsLinked to original sources

bioRxiv2026

Mechanical Signaling Regulates DNA Methylation to Maintain Muscle Stem Cell Quiescence

Skeletal muscle stem cells (MuSCs) reside within a mechanically dynamic niche where they integrate biophysical and biochemical cues to maintain quiescence. Here, we show that substrate stiffness and RhoA-dependent signaling regulate MuSC fate. MuSCs cultured on soft matrices or depleted of RhoA exhibit altered morphology, diminished actomyosin organization, and undergo premature activation. Loss of RhoA reshapes the DNA methylation landscape, leading to widespread changes in gene expression and alternative splicing. Dnmt3a was among the genes transcriptionally downregulated following loss of RhoA signaling. Mechanistically, RhoA maintains Dnmt3a expression by promoting SP1 occupancy at its promoter. Importantly, loss of Dnmt3a in quiescent MuSCs is sufficient to drive activation, identifying Dnmt3a as a key epigenetic effector downstream of mechanical signaling. Together, these findings define a mechanotransduction-epigenetic axis in which RhoA maintains stem cell quiescence by preserving DNA methylation programs through Dnmt3A.

cell biology↗

bioRxiv2022

Transcriptional Responses of Cancer Cells to Heat Shock-Inducing Stimuli Involve Amplification of Robust HSF1 Binding

Responses of cells to signals are increasingly discovered to involve the binding of sequence-specific transcription factors outside of known target genes. We wanted to determine to what extent the genome-wide binding and function of a transcription factor are shaped by the cell type versus the stimulus. To do so, we induced the Heat Shock Response pathway in two distant cell lines with two different stimuli and related the binding of its master regulator HSF1 to nascent RNA and chromatin accessibility. We show that HSF1 binding patterns robustly retain their identity under different magnitudes of activation so that common HSF1 binding is globally associated with stimulus-specific transcription outcomes. HSF1-induced increase in DNA accessibility was modest in scale but occurred predominantly at remote genomic sites. Apart from regulating transcription at existing elements including promoters and enhancers, responses to heat shock may directly engage inactive chromatin.

genomics↗