β-Actin-dependent global chromatin organization and gene expression programs control cellular identity.

Area of Science:

• Cell Biology
• Epigenetics
• Genomics

Background:

• Cell fate and identity are determined by genetic reprogramming and chromatin reorganization.
• The precise mechanisms linking chromatin dynamics to gene regulation during development are not fully understood.
• Actin's role in nuclear processes and its influence on chromatin structure remain areas of active investigation.

Purpose of the Study:

• To investigate the role of beta-actin in chromatin organization and gene expression during cellular differentiation.
• To elucidate the molecular mechanisms by which beta-actin influences genome-wide chromatin structure and gene regulation.
• To determine how beta-actin impacts cellular identity and developmental programs.

Main Methods:

• High-content screening of embryonic fibroblasts from beta-actin knockout mice.
• Analysis of genome-wide H3K9 trimethylation landscape.
• Assessment of Brahma-related gene (Brg)/Brahma-associated factor (BAF) chromatin remodeling complex subunit Brg1 association with chromatin.
• Gene expression profiling and phenotypic analysis.

Main Results:

• Absence of beta-actin leads to major chromatin rearrangements and altered histone modifications (H3K9me3).
• Loss of beta-actin results in the dissociation of Brg1 from chromatin, impacting the BAF complex.
• Upregulation of genes involved in angiogenesis, cytoskeletal organization, and myofibroblast features observed in beta-actin knockout cells.
• Beta-actin dose-dependently influences gene expression and cellular phenotypes.

Conclusions:

• Beta-actin plays a critical role in genome-wide heterochromatin organization through its interaction with the BAF complex.
• Beta-actin is essential for establishing and maintaining cellular identity by controlling gene expression programs.
• Actin's nuclear functions are integral to regulating chromatin structure and directing cell fate decisions.