Gene expression & effects on development Flashcards
Mechanical force can affect gene expression
Mechanotransduction & YAP Activation
Cells sense mechanical forces through integrins, the cytoskeleton, and cell-cell adhesions.
When cells experience high mechanical tension (e.g., stiff ECM, cell stretching, or increased actomyosin contractility), YAP is activated and translocated into the nucleus.
Under low mechanical tension (e.g., soft ECM or cell rounding), YAP is retained in the cytoplasm and degraded.
YAP Nuclear Transport Mechanisms
Passive Diffusion: Small YAP molecules (<40 kDa) may diffuse freely through nuclear pores.
Importin-Mediated Transport: YAP contains nuclear localization signals (NLS), allowing importin proteins to facilitate its nuclear entry.
Nuclear Pore Stretching:
The nuclear envelope is mechanosensitive. When cells experience mechanical forces, the nuclear pores expand, facilitating the transport of larger proteins, including YAP.
Actin cytoskeleton and lamin A/C (nuclear lamina) control nuclear stiffness and pore size.
Increased nuclear tension enhances the permeability of nuclear pores, allowing more YAP to enter.
Gene Expression Activation
Once inside the nucleus, YAP interacts with TEAD transcription factors, leading to the activation of genes involved in proliferation, differentiation, and survival.
This is crucial in stem cell differentiation, tissue regeneration, and even cancer progression.
Regulation of Hox gene expression
Gene clusters can share
enhancers and promoters
