Biophysical Models of Chromatin Structure and Energetics

Alexandre V. Morozov, Rutgers

May 19, 2011 @ 12:00 pm to 01:00 pm

111 Wartik Laboratory

Event Website

Genomic DNA is packaged into chromatin in eukaryotic cells. The fundamental building block of chromatin is the nucleosome, a 147 bp-long DNA segment wrapped around the surface of a histone octamer. Arrays of nucleosomes are folded into filamentous chromatin fibers whose structure and function are poorly understood. Chromatin fiber formation leads to 10-11 bp discretization of linker lengths, typically attributed to the smaller energetic cost of packaging nucleosomes into regular higher-order structures if their rotational setting (defined by the DNA helical twist) is conserved. We have developed a framework for predicting both sequence-specific histone-DNA interactions and the effective two-body potential which accounts for linker length discretization. The contribution of DNA sequence to genome-wide nucleosome positioning has been a subject of much debate in the field. Our approach is based on the analogy between nucleosomal arrays and a one-dimensional fluid of finite-size particles with nearest-neighbor interactions. Contrary to previous expectations, most nucleosomes in S.cerevisiae and C.elegans do not appear to be positioned by periodic dinucleotide patterns that are often thought to facilitate DNA bending around the histone octamer, or by longer sequence motifs such as poly(dA:dT) tracts. Rather, their locations are simply controlled by the dinucleotide content of the underlying DNA sequence. Furthermore, our studies reveal that higher-order chromatin structure plays a crucial role in establishing in vivo nucleosome localization over coding regions, and may be more important for explaining 10-11 bp periodic genome-wide nucleosome positioning patterns than intrinsic histone-DNA sequence preferences.

Contact

Jayanth Banavar
jayanth@phys.psu.edu
814-863-1089