35.2 : Chromosome Duplication

The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.

The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their N-terminal ends protruding out of the core, providing sites for various covalent modifications that regulate chromatin structure and function.

During replication, as the DNA unwinds, parental nucleosomes are disrupted, and histone proteins are released. As replication progresses and daughter strands form, the parental histones and the additional histone proteins synthesized during S-phase are assembled, allowing the formation of nucleosomes.

The post translational modifications of the histones and other epigenetic domains in the DNA are also faithfully reproduced in the daughter genome.

Chromatin structure influences gene expression

Within a cell, the major portion of the genome remains inaccessible to transcription factors, as the regulatory and coding DNA sequences exist mostly concealed within the nucleosomes. For a gene to express, it is necessary to create accessible sites for transcription factors to bind and also to modify the histones to reorganize the chromatin structure and create an environment permissive for transcription.

Specific regulatory factor complexes are involved in opening up localized regions of the chromatin by displacement or disruption of nucleosomes. Post-translational modifications of the histone tail serve to maintain either an active or inactive transcriptional state. Specific modifications at the histone tail can ease the level of DNA compaction, facilitating the destabilization and displacement of nucleosomes, providing access for transcription machinery to influence gene expression.