Mechanisms of sequence-dependent chromatin remodeling

Eukaryotic genomes are packaged into chromatin, which restricts access to the DNA.

Key genomic processes therefore involve the rearrangement of chromatin by ATP-dependent chromatin remodeling enzymes (remodelers), which actively place and reorganize nucleosomes. The precise positioning of nucleosomes plays a crucial role in regulating transcription, replication, and DNA repair. DNA sequence impacts this nucleosome architecture by affecting the activity of remodelers.

However, what mechanisms underlie this critical sequence dependence in remodeling remains unknown.

Here, we propose to address this longstanding question by directly observing nucleosome remodeling by select remodelers as a function of sequence at the genome scale, which cannot be achieved with currently existing methods.

We aim to address this major challenge by utilizing our novel high-throughput MUSCLE (MUltiplexed Single-molecule Characterizations at the Library scalE) platform that combines single-molecule measurements of complex dynamics with next-generation sequencing.

We expect to gain major insights into the mechanisms of sequence-dependent remodeling and its role in the establishment of chromatin architecture.