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Background：
Histone H4 assembles with H3 to form H3-H4 tetramer, the core scaffold of nucleosomes. Lysine monomethylation is a reversible epigenetic modification modulated by methyltransferases and demethylases. Methylation recruits specific reader proteins to modulate chromatin assembly, gene transcription and genome stability. Distinct lysine methylation sites on H4 exert different regulatory functions. H4K5 monomethylation (H4K5me1) exists on newly synthesized histones after DNA replication. It synergizes with H4 tail acetylation to promote post-replication nucleosome maturation and maintain chromatin accessibility for transcription machinery. This modification also participates in mild DNA damage response to assist chromatin remodeling at lesion sites. H4K12 monomethylation (H4K12me1) is a characteristic marker of nascent histone H4, catalyzed by histone methyltransferases during chromatin assembly. It balances chromatin compaction and transcription initiation at housekeeping gene promoters. Under genotoxic stress, H4K12me1 accumulates at double-strand break loci to coordinate repair complex recruitment.
