Distinct macroH2A variant dynamics reveal temporal mH2A2 displacement at cell-cycle regulatory elements

While mH2A1 has been reported to undergo cell-cycle dependent deposition, whether mH2A2 displays similar behavior remains largely unknown. Here, using native ChIP-seq in synchronized Huh-7 cells, we profiled both mH2A1 and mH2A2 across G1/S and G2/M states.

We found that although the enriched domains of two mH2A variants overlapped extensively across the genome, their local enrichment patterns diverged substantially, particularly at gene bodies. mH2A2 domains were largely stable across the cell-cycle, yet a small subset displayed phase-specific deposition and displacement. Based on the mH2A2 deposition levels across the cell-cycle, we classified mH2A2 domains into five categories: invariant, G1/S-higher, G1/S-unique, G2/M-higher, and G2/M-unique.