Major Determinants of Nucleosome Organization

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

Otro; NIH Research Festival; 2015

NIH

Genome-wide nucleosome mapping experiments suggest a conserved nucleosome organization near gene promoters, consisting of regular nucleosome arrays on the gene bodies and a nucleosome-depleted region (NDR) immediately upstream of the transcription start site (TSS). This organization is common among different species. We study the major determinants of nucleosome organization in vivo, and the common principles that can explain the similarities in nucleosome distribution among different organisms. We show that in yeast, the DNA sequence alone is not able to generate neither the proper NDRs, nor the nucleosome phasing that is observed in vivo. Transcription and chromatin remodeling factors play key roles in establishing the steady state distribution of the nucleosomes. We analyze the roles of four remodelers (Isw1, Isw2, Chd1 and RSC) in chromatin organization, by mapping the nucleosome positions in yeast strains lacking one, two, three or all four remodelers. Although nucleosome organization at the majority of yeast genes conforms to the overall average distribution across the genome, many other genes have a nucleosome distribution that differs from the average pattern. The position of the NDR relative to the TSS varies from gene to gene, and nucleosome arrays at individual genes can also have different spacing between nucleosomes. We construct a minimal model which can explain the nucleosome phasing at the 5' ends of the genes by competition between histones and other DNA-binding proteins, in a transcription-dependent way. We also propose a model for ATP-dependent nucleosome positioning by the chromatin remodeling enzymes.