Priming chromatin for segregation: functional roles of mitotic histone modifications

Abstract

Posttranslational modifications (PTMs) of histone proteins are important for various cellular processes including regulation of gene expression and chromatin structure, DNA damage response and chromosome segregation. Here we comprehensively review mitotic histone PTMs, in particular phosphorylations, and discuss their interplay and functions in the control of dynamic protein-protein interactions as well as their contribution to centromere and chromosome structure and function during cell division. Histone phosphorylations can create binding sites for mitotic regulators such as the chromosomal passenger complex, which is required for correction of erroneous spindle attachments and chromosome bi-orientation. Other histone PTMs can alter the structural properties of nucleosomes and the accessibility of chromatin. Epigenetic marks such as lysine methylations are maintained during mitosis and may also be important for mitotic transcription as well as bookmarking of transcriptional states to ensure the transmission of gene expression programs through cell division. Additionally, histone phosphorylation can dissociate readers of methylated histones without losing epigenetic information. Through all of these processes, mitotic histone PTMs play a functional role in priming the chromatin for faithful chromosome segregation and preventing genetic instability, one of the characteristic hallmarks of cancer cells.

The histone H4 lysine 20 demethylase DPY-21 regulates the dynamics of condensin DC binding

“…Furthermore, condensin DC and dpy-21 are also required for lower levels of histone H3 lysine 27 acetylation (H3K27ac) on the X chromosome ( Street et al, 2019 ). An increase of H4K20me1 and decreased acetylation mirror the histone modification changes on metazoan mitotic chromatin ( Schmitz et al, 2020 ), providing a link between canonical condensin and condensin DC binding to chromatin.…”

A Peak of H3T3 Phosphorylation Occurs in Synchrony with Mitosis in Sea Urchin Early Embryos

“…However, despite the fact that Cyclins were first described in sea urchin embryos [11], little is known in these animals about the identity of the Cyclin B/CDK1 targets, especially at the chromatin level. 2 of 14 In fact, although the regulation of histone activity via post-translational modifications is likely to play a central role during chromatin condensation and chromatid separation [12,13], the dynamics of these modifications and their functional significance have not been studied in depth during sea urchin development [14].…”

LiveCellMiner: A new tool to analyze mitotic progression

“…In turn, the abnormal fluctuations in the orientation of metaphase chromatin indicates faulty function of the cortical network and/or defective astral microtubules emanating from the spindle poles ([ 55 , 56 ]; see [ 61 ] for review). In the case of LSD1 downregulation, where no metaphase chromatin rotation is observed, the early mitotic delay might arise from defects in chromatin methylation impairing correct chromosome segregation ([ 62 ]; see [ 63 ] for review), and might reflect unbalances in the expression of three major players of the mitotic control: PLK1[ 64 ], BUBR1 and MAD2[ 65 ], whose transcriptional regulation is influenced by LSD1. Likewise, the absence of rotation of the metaphase plate in RecQL4-downregulated cells suggests that the delay in early mitotic progression is not due to malfunction of the astral microtubules and/or cortical network.…”