Chromosome organization and chromatin modification: influence on genome function and evolution

Histone modifications of nucleosomes distinguish euchromatic from heterochromatic chromatin states, distinguish gene regulation in eukaryotes from that of prokaryotes, and appear to allow eukaryotes to focus recombination events on regions of highest gene concentrations. Four additional epigenetic mechanisms that regulate commitment of cell lineages to their differentiated states are involved in the inheritance of differentiated states, e.g., DNA methylation, RNA interference, gene repositioning between interphase compartments, and gene replication time. The number of additional mechanisms used increases with the taxon's somatic complexity. The ability of siRNA transcribed from one locus to target, in trans, RNAi-associated nucleation of heterochromatin in distal, but complementary, loci seems central to orchestration of chromatin states along chromosomes. Most genes are inactive when heterochromatic. However, genes within beta-heterochromatin actually require the heterochromatic state for their activity, a property that uniquely positions such genes as sources of siRNA to target heterochromatinization of both the source locus and distal loci. Vertebrate chromosomes are organized into permanent structures that, during S-phase, regulate simultaneous firing of replicon clusters. The late replicating clusters, seen as G-bands during metaphase and as meiotic chromomeres during meiosis, epitomize an ontological utilization of all five self-reinforcing epigenetic mechanisms to regulate the reversible chromatin state called facultative (conditional) heterochromatin. Alternating euchromatin/heterochromatin domains separated by band boundaries, and interphase repositioning of G-band genes during ontological commitment can impose constraints on both meiotic interactions and mammalian karyotype evolution.