Cell cycle control of chromatin creates a therapeutic window for epigenetic therapy in tumors
Hayatigolkhatmi, K.; Valzelli, R.; Ceccacci, E.; Hosseini, A.; El Menna, O.; Romanenghi, M.; Pallavicini, I.; Soda, E.; Ejlli, O.; Villa, E.; Falvo, P.; Blanco, E.; Aranda, S.; Barkhordar, R.; Soriani · cancer biology · 2026-09-06 · 原文
DOI：10.64898/2026.09.03.748889作者：15 位
The relationship between cell cycle length and differentiation competence is well established in developmental biology, particularly in embryonic stem cells, where a short G1 phase maintains pluripotency and G1 lengthening permits lineage commitment. Whether this principle operates in cancer cells, where the cell cycle is deregulated and G1 is frequently shortened, and whether it can be pharmacologically exploited for therapy, has not been tested. Here we show that the duration of G1 is a causal determinant of chromatin state in cancer cells and that extending G1 creates a therapeutic window for epigenetic drugs. Using acute myeloid leukemia (AML) as a model, we demonstrate that low-dose palbociclib, at concentrations well below those required for cytostatic arrest, extends G1 without halting proliferation. This modest prolongation reshapes the histone modification landscape: repressive marks (H3K9me2/3, H4K20me2/3) increase while acetylation decreases, and chromatin accessibility rises broadly in the euchromatic compartment. Naturally slow-cycling AML lines share this epigenetic signature regardless of their oncogenic driver mutations, and pharmacologically extending G1 in fast-cy
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1. 人话版
The relationship between cell cycle length and differentiation competence is well established in developmental biology, particularly in embryonic stem cells, where a short G1 phase maintains pluripotency and G1 lengthening permits lineage commitment.
Whether this principle operates in cancer cells, where the cell cycle is deregulated and G1 is frequently shortened, and whether it can be pharmacologically exploited for therapy, has not been tested.
2. 领域脉络
本文类目：cancer biology，属于其所在研究脉络的最新进展。
3. 机制拆解
摘要未展开方法细节——精读时重点看方法/模型部分。
4. 证据与数字
Here we show that the duration of G1 is a causal determinant of chromatin state in cancer cells and that extending G1 creates a therapeutic window for epigenetic drugs.
Using acute myeloid leukemia (AML) as a model, we demonstrate that low-dose palbociclib, at concentrations well below those required for cytostatic arrest, extends G1 without halting proliferation.
This modest prolongation reshapes the histone modification landscape: repressive marks (H3K9me2/3, H4K20me2/3) increase while acetylation decreases, and chromatin accessibility rises broadly in the euchromatic compartment.
5. 反例与边界
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6. 跨领域连接与意外收获
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8. 术语表
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