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Background:Combinatorial histone post-translational modifications orchestrate chromatin structure and cell cycle-dependent epigenetic regulation. H3T6pK9me1 is a dual epigenetic modification of histone H3, including threonine 6 phosphorylation (T6p) and lysine 9 monomethylation (K9me1). H3K9me1 is a moderate repressive marker distributed in mammalian chromatin, while H3T6p is a mitosis-specific phosphorylation modified mainly by PKC kinases. This dual mark is dynamically regulated during cell cycle. Mitotic T6 phosphorylation occurs on H3K9me1-modified histones, rearranges the binding profile of chromatin reader proteins, and supports orderly chromosome condensation and segregation, while retaining the intrinsic H3K9me1 epigenetic information. Dysregulation of H3T6pK9me1 impairs mitotic chromatin remodeling and epigenetic inheritance, leading to genomic instability.
