Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Topology of Eukaryotic Chromatin
Little is known about how nucleosomes are arranged into higher-order structures in vivo, even though the efficiency and precision of cell division imply a high level of structural organization. The current view of eukaryotic chromatin organization assumes that nucleosomal particles self-organize by association into higher-order structures in a hierarchical manner. The so-called 30-nm fiber structure plays a prominent role in these models. These assumptions do not agree, among others, with the observed mechanical properties of chromatin, or with microscopic in situ, and in vitro, observations of chromatin in its native state and also with the distributive character of chromatids? individualization.
We have re-analyzed published observations and experimental data from the last 50 years of work on eukaryotic chromatin for consistency between them and basic laws of physics and evolution. Following this work, we propose to abandon the associative paradigm for eukaryotic chromatin organization. Instead we propose organization involving a group of DNA-based, recursive topological restraints. These are created by ATP-dependent remodeling complexes in kinetically controlled processes. Nucleosomal particles play an important role in this model serving as memory markers for remodeling complexes. An outline of the theory is presented at preprint server. We will discuss the novel paradigm of eukaryotic chromatin organization, its agreement with experimental data, its role in explaining the action of distant-cis acting elements in transcription and other consequences for biology.