Epigenetics Theme, Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Genetics Training Program, University of Wisconsin-Madison, Madison, WI 53715, USA.
Epigenetics Theme, Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
Stem Cell Reports. 2018 Feb 13;10(2):627-641. doi: 10.1016/j.stemcr.2017.12.016.
The heterochromatin protein 1 (HP1) family is involved in various functions with maintenance of chromatin structure. During murine somatic cell reprogramming, we find that early depletion of HP1γ reduces the generation of induced pluripotent stem cells, while late depletion enhances the process, with a concomitant change from a centromeric to nucleoplasmic localization and elongation-associated histone H3.3 enrichment. Depletion of heterochromatin anchoring protein SENP7 increased reprogramming efficiency to a similar extent as HP1γ, indicating the importance of HP1γ release from chromatin for pluripotency acquisition. HP1γ interacted with OCT4 and DPPA4 in HP1α and HP1β knockouts and in H3K9 methylation depleted H3K9M embryonic stem cell (ESC) lines. HP1α and HP1γ complexes in ESCs differed in association with histones, the histone chaperone CAF1 complex, and specific components of chromatin-modifying complexes such as DPY30, implying distinct functional contributions. Taken together, our results reveal the complex contribution of the HP1 proteins to pluripotency.
异染色质蛋白 1 (HP1) 家族参与维持染色质结构的各种功能。在小鼠体细胞重编程过程中，我们发现 HP1γ 的早期耗竭会减少诱导多能干细胞的产生，而晚期耗竭则会增强这一过程，同时伴随着从着丝粒到核质的定位和与伸长相关的组蛋白 H3.3 的富集。异染色质锚定蛋白 SENP7 的耗竭同样会增加重编程效率，这与 HP1γ 的效果相似，表明 HP1γ 从染色质上释放对于获得多能性非常重要。HP1γ 在 HP1α 和 HP1β 敲除以及 H3K9 甲基化耗尽的 H3K9M 胚胎干细胞 (ESC) 系中与 OCT4 和 DPPA4 相互作用。ESC 中的 HP1α 和 HP1γ 复合物在与组蛋白、组蛋白伴侣 CAF1 复合物以及染色质修饰复合物的特定成分（如 DPY30）的关联方面存在差异，这暗示了它们具有不同的功能贡献。总之，我们的研究结果揭示了 HP1 蛋白在多能性中的复杂贡献。
