A mathematical model of CENP-A incorporation in mammalian centromeres

•A first mathematical model for CENP-A incorporation at mammalian centromeres is presented.•The model produces results that are consistent with experimental findings.•The modelling process highlights gaps in what is currently known about the CENP-A deposition pathway.•The sensitivity of the model output to the values of some of its parameters is investigated.•The model is capable of resolving apparent conflicts in experimental evidence.

Centromere Protein A (CENP-A) is a histone H3 variant found at mammalian centromeres. Unlike canonical histones which are incorporated at centromeres in S phase, CENP-A is deposited at centromeric chromatin in G1. Although recent studies have elucidated many of the molecular details associated with the CENP-A incorporation pathway, some aspects of the process are still not fully understood. CENP-A incorporation in G1 requires multiple assembly factors for its recruitment and maintenance. In this study, the first mathematical model of the CENP-A incorporation pathway is developed. The model is based on what is currently known about the pathway and is calibrated by comparing numerical simulations with experimental observations taken from the literature. The model succinctly collates a large body of knowledge accumulated in recent decades concerning the pathway and produces results that are consistent with experimental findings. It identifies possible gaps in what is currently known about the pathway and suggests possible directions for future research. It is envisaged that the model will be expanded upon and improved as more information concerning the pathway comes to light.

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