How is our genetic information utilized to achieve this feat? In part, it involves the hierarchical regulation of gene expression programs in which a small number of lineage-specifying master transcription factors activate or repress a large number of downstream targets (Weintraub, 1993; Nutt et al., 1999; Stoykova et al., 2000; Boyer et al., 2005). However, these concerted changes in gene expression profile must occur within the physical dimensions of the cell’s 5-micron nucleus that necessitates extraordinary compaction of DNA. The two billion base pairs of the human genome would total two meters in length if extended, but in the nucleus they are packaged around histone octamers and further compacted to form chromatin (Kornberg, 1974). The degree of compaction is not uniform across all chromatin loci, and while ‘open’ (euchromatic) regions are accessible to nuclear factors, ‘closed’ or repressed (heterochromatic) regions are unable to be activated. Thus, there must be dynamic interplay between chromatin regulation and the actions of other nuclear factors throughout development.
