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

ABSTRACT: MacroH2A (mH2A) variants have traditionally been viewed as transcriptional repressors, with mH2A2 specifically implicated in modulating enhancer accessibility to suppress transcriptional programs. 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. Among them, G1/S-unique mH2A2 domains were specifically enriched in the active A compartment, and the potential regulatory elements within them exhibited lower chromatin accessibility. These sites were preferentially bound by cell-cycle regulatory factors and were linked to genes involved in mitotic progression. Collectively, our findings reveal that mH2A2 undergoes selective displacement from regulatory elements during mitotic entry, supporting a model in which mH2A2 functions as a context-dependent regulator of chromatin accessibility during cell-cycle progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE337818 | GEO | 2026/07/12

REPOSITORIES: GEO