Dynamic Changes of Histone H1 Variants in Drug-Induced Senescence

Background/Objectives: Cellular senescence is a stress-induced state of irreversible cell cycle arrest triggered by diverse molecular stimuli. It is characterized by distinct phenotypic alterations, including the senescence-associated secretory phenotype (SASP), profound chromatin remodeling, and morphological changes. While senescent cells accumulate during physiological aging, they are also prevalent in pathological contexts such as cancer. Histone H1 is a crucial regulator of chromatin organization and gene expression, and emerging evidence suggests that its content and nuclear distribution change dynamically during senescence.

Methods

Here, we investigated the expression and localization dynamics of six somatic H1 variants (H1.0, H1.2 to H1.5, and H1X) upon senescence induction in T47D breast cancer cells, evaluating their correlation with chromatin structural alterations, repetitive element expression, and interferon response activation. Senescence was triggered using doxorubicin, a topoisomerase inhibitor, among other drugs tested, which was confirmed by the accumulation of standard senescence markers (ß-galactosidase activity, p21CIP1/WAF1, H3K9me3, and γH2AX).