Julia R. Widom

TL;DR: In this paper, a set of highest affinity molecules were selected, cloned and sequenced, their affinities (free energies) for histone octamer in nucleosome reconstitution measured, and their ability to position nucleosomes in vitro assessed by native gel electrophoresis.

TL;DR: Evidence is presented for a mechanism by which regulatory proteins may gain access to their target DNA sequences in chromatin, and new mechanisms for cooperativity (synergy) in regulatory protein binding and for active invasion of nucleosomes are offered.

TL;DR: It is found that the strongest natural positioning sequences have affinities for histone binding and nucleosome formation that are sixfold or more lower than those possessed by many of the selected non-natural sequences.

TL;DR: The progressive decrease in equilibrium constant with distance inside the nucleosomes supports the hypothesis that access to sites internal to a nucleosome is provided by progressive (transient) release of DNA from the octamer surface, starting from one end of theucleosomal DNA.

TL;DR: The model shows that nucleosomes are intrinsically dynamic, transiently exposing their DNA to allow sequence-specific protein binding even at buried sites, and provides a mechanism for cooperativity (synergy) in the binding of two or more proteins to sites on a single nucleosome, even if those proteins do not interact directly with each other in any way.