Involvement of condensin in cellular senescence through gene regulation and compartmental reorganization

Area of Science:

• Cell Biology
• Genomics
• Molecular Biology

Background:

• Cellular senescence is a state of irreversible cell cycle arrest triggered by various stressors.
• Senescence involves significant changes in gene expression and the 3D genome organization.
• The role of specific protein complexes in regulating these changes remains an active area of research.

Purpose of the Study:

• To investigate the role of the human condensin II complex in cellular senescence.
• To elucidate the mechanisms by which condensin II influences genome organization and gene regulation during senescence.
• To determine the impact of condensin II on senescence-associated gene expression.

Main Methods:

• Induction of oncogene-induced senescence (OIS) and replicative senescence (RS) in human cells.
• Analysis of 3D genome organization, including compartmentalization (A and B compartments).
• Assessment of gene expression, focusing on senescence-associated genes (SASP, p53 targets).
• Depletion of condensin II complex to evaluate its functional role.

Main Results:

• Condensin II complex is involved in the reorganization of euchromatic (A) and heterochromatic (B) compartments during senescence.
• Both OIS and RS exhibit transitions between A and B compartments, with B-to-A transitions being more frequent and affecting a significant portion of the genome.
• Condensin II is enriched in A compartments and facilitates B-to-A compartmental transitions.
• Depletion of condensin II impairs the activation of senescence genes and reduces senescence markers.

Conclusions:

• Condensin II reinforces euchromatic A compartments and promotes B-to-A transitions during senescence.
• These genomic reorganization events mediated by condensin II are coupled to the optimal expression of senescence genes.
• The study highlights condensin II as a key contributor to the molecular mechanisms underlying cellular senescence.