Extended Data Fig. 5. Model to explain equalization of epigenetic differences and subsequent memory.

a, Assumptions used for the modeling. b, Epigenetic inheritance of CENP-A as determined in cycling somatic cells in culture by replication coupled dilution and G1 reloading. c, Example calculation and graph for CENP-A assembly in the first two embryonic cell cycles for progeny of a WT × WT cross. For simplicity, initial CENP-A levels are set to 100 and 50 on the maternal and paternal centromeres, respectively, based on our measurements in zygotes (Fig. 3c). At each S-phase, CENP-A levels are diluted by half on each centromere, and we assume equal assembly on maternal and paternal centromeres in the following G1. Assembly in the first cell cycle depends on the maternal pool, set to 100 for a zygote from a WT female, giving an increase of 50 on both maternal and paternal centromeres. Assembly in the second cell cycle depends on the zygotic pool, which is set to 100 for a WT zygotic genotype. d, Graphs from similar calculations as b, for the designated crosses. Initial CENP-A levels are set to 50 for maternal centromeres from Cenpa^+/− mothers and 40 for paternal centromeres from Cenpa^+/− fathers, based on our measurements (Fig. 1c and Fig. 2c). Arrows indicate equal assembly on maternal and paternal centromeres. In the first cell cycle, assembly is from a maternal pool of 100 (black arrows) or 50 (yellow arrows) for WT or Cenpa^+/− mothers, respectively. In the second cell cycle, assembly is from a zygotic pool of 100 (purple arrows), reflecting a WT zygotic genotype. Calculations show equalization by the four-cell stage in all crosses. Furthermore, crosses with reduced maternal contribution (H♀) equalize to a lower level, which is then remembered through development. Source numerical data are available in source data.