Tamar Schlick, Ph.D.
, professor, New York University
Deciphering chromosome tertiary organization is essential for understanding how genetic information is replicated, transcribed, silenced, and edited to control basic life processes. Many experimental studies of chromatin using nucleosome structure determination, ultra-structural techniques, single-force extension studies, and analysis of chromosomal interactions have revealed important chromatin characteristics as a function of various internal and external conditions, such as looping, compaction, and compartmentalization. Modeling studies, anchored to high-resolution nucleosome models, have explored related questions systematically. In this talk, Schlick will describe multiscale computational approaches for chromatin modeling at nucleosome resolution and recent mesoscale chromatin simulations that incorporate key physical parameters such as nucleosome positions, linker histone binding, and acetylation marks to 'fold' in silico the Hox C gene cluster. The folded gene reveals a contact hub that connects an acetylation-rich with a linker histone-rich region. Such chromatin modeling techniques open the way to other computational folding of genes and genomes. Moreover, the resulting folded system emphasizes the heterogeneity of chromatin fibers and hierarchical looping motifs, and underscores how nucleosome positions in combination with epigenetic marks and linker histone binding direct the tertiary folding of fibers and genes to perform their cellular tasks. These chromatin architecture findings have important implications on many important processes including cell differentiation, gene regulation, and disease progression.