Question

Mention what modification patterns in histones are present in nucleosome during mitosis.

Explain how such modification patterns affect chromatin structure in mitosis

Answer 1

Chromatin is the state in which DNA is packaged within the cell. The nucleosome is the fundamental unit of chromatin and it is composed of an octamer of the four core histones (H3, H4, H2A, H2B) around which 147 base pairs of DNA are wrapped. The core histones are predominantly globular except for their N-terminal “tails,” which are unstructured. A striking feature of histones, and particularly of their tails, is the large number and type of modified residues they possess. There are at least eight distinct types of modifications found on histones. We have the most information regarding the small covalent modifications acetylation, methylation, and phosphorylation.

Phosphorylation. Phosphorylation is one of the best understood post-translational histone modifications. In mammals and many other organisms, Histone H3 is highly phosphorylated when the cell enters mitosis. Serine 10 of histone H3 (H3S10) is well characterized to be tightly associated with mitosis in many organisms. This phosphorylation is believed to be a crucial step in the high orders of chromatin condensation and compaction, which are essential for subsequent chromosome congression and segregation during mitosis.

Acetylation. Although changes in histone acetylation are mostly associated with active gene transcription, they also occur during mitosis. There is an overall reduction in histone acetylation levels during mitosis, consistent with the repressed transcriptional activity during mitosis. Thus, general acetylation levels of histone H2A, H2B, H3 and H4 are all reduced during mitosis. Histone deacetylation, a biochemical process that counteracts acetylation, is critical for mitosis since inhibition of histone deacetylase activities increases chromosomal instability by dislocalizing mitotic checkpoint proteins from the kinetochores and prolonging mitotic arrest in mammalian cells. The reduced histone acetylation level during mitosis may serve to neutralize negative charges of DNA, thereby facilitating chromatin super-condensation.

Methylation. Histone methylation was once considered a stable post translational modification that is primarily associated with regulation of gene transcription. The dynamic regulation of histone methylation and its function in the cell cycle as well as in regulation of gene expression was not fully appreciated until the discovery of histone demethylases. Methylation levels of histone H3 remain high and constant throughout the cell cycle, and is correlated with a high activity of histone H3 methyl transferase (HMT) in mammalian cells.

Ubiquitination. Ubiquitination is a modification during which heat-stable ubiquitin is covalently attached to specific Lysine residues of target proteins. This modification either regulates the function or provides a tag for degradation of target proteins. Growing evidence indicates a direct involvement of histone ubiquitination in normal mitosis.

Other modifications. Histones are also subject to other types of modifications such as sumoylation, biotinylation, ADP ribosylation, proline isomerization and deimination. The information on these types of modifications is rather limited and a direct association of these modifications with mitosis and meiosis remains to be explored.