Nucleosomal DNA has topological memory.

Area of Science:

• Molecular Biology
• Genomics
• Biophysics

Background:

• Chromosome architecture involves DNA topology constrained by nucleosomes.
• Nucleosomes stabilize negative DNA supercoils, with a typical DNA linking number difference (∆Lk) of -1.26.
• The uniformity of this nucleosomal DNA topology constraint across the genome remains largely unknown.

Purpose of the Study:

• To investigate whether nucleosomes restrain a uniform DNA linking number difference (∆Lk) across different genomic regions.
• To determine if the genomic origin of a nucleosome influences its DNA topology.
• To assess if nucleosome DNA topology is imprinted by its native chromatin context.

Main Methods:

• Calculation of ∆Lk restrained by over 4000 yeast nucleosomes.
• Utilizing Topo-seq, a high-throughput method to analyze DNA topology.
• Insertion of individual nucleosomes into circular minichromosomes for topological analysis via gel electrophoresis.

Main Results:

• Nucleosomes exhibit distinct ∆Lk values based on their genomic origin.
• Observed ∆Lk values varied in gene bodies (-1.29), intergenic regions (-1.23), rDNA genes (-1.24), and telomeric regions (-1.07).
• Nucleosomes near transcription start and termination sites showed unique DNA topologies.

Conclusions:

• Nucleosome DNA topology is not uniform and is significantly influenced by its native chromatin context.
• The topological imprinting on nucleosomes persists even when they are relocated from their original genomic position.
• This finding provides insights into the dynamic regulation of DNA topology within the genome.