Determinants of nucleosome organization

RAZVAN V CHEREJI; JOSEFINA OCAMPO; TARA L BURKE; DAVID J CLARK

Bethesda

Simposio; NCI Symposium on Chromosome Biology: Chromatin, ncRNA, Methylation and disease; 2015

National Cancer Institute-NIH

Nucleosomes pack the DNA within the very crowded eukaryotic nuclei, but they also control the access to regu- latory regions along the genome. We study the relationship between nucleosome organization and transcriptional regu- lation. In vivo, nucleosome form regular arrays on the gene bodies and a nucleosome-depleted region near transcription start sites. By in vitro nucleosome reconstitution, we show that DNA sequence has a minor role in generating this configuration, and we identify the major determinants of nucleosome organization. Non-histone proteins bind to gene promoters and compete with histone binding, creating nucleosome depleted regions; chromatin remodelers organize the nucleo- somes in regular arrays; and transcription disrupts the arrays of nucleosomes. We also study rigorous statistical mechanics models which explain the nucleosome phasing relative to the transcription start sites observed in vivo, and we propose a model for the ATP-dependent active nucleosome positioning by chromatin remodelers.