Priming chromatin for segregation: functional roles of mitotic histone modifications
M. Lienhard Schmitz, Jonathan M.G. Higgins, Markus Seibert
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.