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18.2:

Duplicación de la estructura de la cromatina

JoVE Core
Molecular Biology
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JoVE Core Molecular Biology
Duplication of Chromatin Structure

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The genetic material, the DNA, in a eukaryotic cell exists inside the nucleus as linear structures called the chromosomes. Within the chromosomes, the double-stranded DNA primarily wraps around octameric nuclear proteins called histones to form nucleosomes. Several non-histone proteins also associate with the DNA, assisting in DNA packaging. These nucleosomes and non-histone proteins arrange to form coils which further fold into loops, in an array, forming packed chromatin. The extent of chromatin compaction enables extremely long DNA to fit inside the nucleus. During M phase, chromatin further coils to form the condensed chromosomes. Chromosome duplication involves duplicating the entire chromatin structure, so the DNA and chromatin-associated proteins are all duplicated. The production of histones is increased to generate the additional proteins required for packaging the newly synthesized DNA into chromosomes. Replicating the exact chromatin structure of the duplicated chromosome is vital for gene regulation.  Within the chromosomes, the level of chromatin packaging is not always uniform. Chromosomes contain regions with tightly packed chromatin called heterochromatin and regions with loosely packed chromatin called euchromatin. Heterochromatin DNA is inaccessible to the transcription machinery, and hence genes in those regions are not regularly transcribed. In contrast, the DNA within the euchromatin is more accessible, and thus genes in these regions can be transcribed.    This structural and functional significance of chromatin makes it crucial that the entire chromatin structure is reproduced accurately during chromosome duplication.

18.2:

Duplicación de la estructura de la cromatina

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.

Suggested Reading

  1. Groth, Anja, Walter Rocha, Alain Verreault, and Geneviève Almouzni. “Chromatin Challenges during DNA Replication and Repair.” Cell 128 (4)2007: 721–33. [Source]
  2. Margueron, Raphaël, and Danny Reinberg. “Chromatin Structure and the Inheritance of Epigenetic Information.” Nature Reviews Genetics 11 (4)2010: 285–96. [Source]