Comprehensive profiling of chromatin occupancy dynamics through the cell cycle.

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• DNA-binding factors establish chromatin context for DNA-templated processes.
• Previous research focused on external perturbations, lacking cell-cycle specific chromatin dynamics.
• Understanding cell-cycle chromatin dynamics is crucial for gene regulation.

Purpose of the Study:

• Investigate the interplay between cell-cycle-regulated chromatin dynamics and transcription.
• Profile genome-wide chromatin occupancy and transcriptome across cell cycles.
• Develop a model to predict transcript dynamics using chromatin data.

Main Methods:

• Utilized Saccharomyces cerevisiae as a model organism.
• Performed time-series profiling of chromatin occupancy (MNase-seq) and transcriptome (RNA-seq) over two cell cycles.
• Employed entropy as a measure of nucleosome organization and developed a Gaussian process statistical model.

Main Results:

• Identified a small subset of cell-cycle-regulated genes with matching protein occupancy and expression dynamics.
• Discovered widespread, transcription-independent chromatin changes during cell-cycle progression.
• Observed nucleosome disruption in S phase and re-organization in M phase, with exceptions for highly transcribed mitotic genes.

Conclusions:

• Chromatin dynamics during the cell cycle are complex and not always directly tied to gene expression.
• Transcription-independent chromatin reorganization occurs during cell division.
• The developed model improves prediction of transcript dynamics using chromatin features.