Large-scale chromatin organization: The good, the surprising, and the still perplexing

Traditionally large-scale chromatin structure has been studied by microscopic approaches, providing direct spatial information but limited sequence context. In contrast, newer 3C (chromosome capture conformation) methods provide rich sequence context but uncertain spatial context. Recent demonstration of large, topologically linked DNA domains, hundreds to thousands of kb in size, may now link 3C data to actual chromosome physical structures, as visualized directly by microscopic methods. Yet, new data suggesting that 3C may measure cytological rather than molecular proximity prompts a renewed focus on understanding the origin of 3C interactions and dissecting the biological significance of long-range genomic interactions.