Single-chromosome dynamics reveals locus-dependent dynamics and chromosome territory orientation

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Dynamic chromatin organization regulates DNA accessibility and transcription.
• Regulation of chromatin dynamics, nuclear orientation, and compaction remains unclear.
• Previous studies suggest locally confined chromatin dynamics contribute to nuclear motion.

Purpose of the Study:

• To characterize dynamics of specific genomic loci using real-time single-particle tracking.
• To determine compaction levels of large human chromosomal domains.
• To understand regulation of dynamics, nuclear orientation, and compaction along a single chromosome.

Main Methods:

• CRISPR-based real-time single-particle tracking.
• Polymer models for analyzing genomic loci dynamics.
• Determination of compaction levels in human chromosomal domains.

Main Results:

• Chromosome compaction varies during interphase, with differential compaction between chromosome 19 arms.
• Genomic loci dynamics are subdiffusive and depend on chromosomal regions and transcriptional states.
• Negligible correlation found between locus-dependent nuclear localization and mobility; strong tethering at pericentromeres observed.

Conclusions:

• Chromatin dynamics and compaction are region- and transcription-dependent.
• Pericentromeric regions exhibit strong tethering, suggesting local condensation or organelle association.
• A 'guided radial model' is proposed for nuclear orientation of chromosome 19's long arm.