Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance.
Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance.
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DOI：
10.1016/j.stemcr.2017.12.016
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发表时间：
2018-02-13
影响因子：
5.9
通讯作者：
Sridharan R
中科院分区：
文献类型：
--
作者：
Zaidan NZ;Walker KJ;Brown JE;Schaffer LV;Scalf M;Shortreed MR;Iyer G;Smith LM;Sridharan R
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，早期消耗HP 1 γ减少了诱导多能干细胞的产生，而晚期消耗增强了该过程，伴随着从着丝粒到核质定位的变化和延长相关的组蛋白H3.3富集。异染色质锚定蛋白SENP7的消耗增加重编程效率至与HP 1 γ相似的程度，表明HP 1 γ从染色质释放对于多能性获得的重要性。在HP 1 α和HP 1 β敲除以及H3 K9甲基化缺失的H3 K9 M胚胎干细胞（ESC）系中，HP 1 γ与OCT 4和DPPA 4相互作用。胚胎干细胞中的HP 1 α和HP 1 γ复合物与组蛋白、组蛋白伴侣CAF1复合物和染色质修饰复合物的特定组分如DPY 30的相关性不同，这意味着不同的功能贡献。总之，我们的结果揭示了HP1蛋白对多能性的复杂贡献。HP 1 γ与OCT 4和DPPA 4相互作用，不依赖于HP 1 α、HP 1 β和H3K9甲基化。Sridharan及其同事在重编程和多能性中对异染色质蛋白1（HP1）家族进行了蛋白质组学表征。HP 1 γ或其相互作用伴侣SENP 7（将其锚定在异染色质上）的消耗增加了iPSC的产生。在多能细胞中，HP 1 γ是高度核质性的，并且富含组蛋白H3.3。HP 1 γ与OCT 4和DPPA 4相互作用，不依赖于HP 1 α、HP 1 β和H3K9甲基化。HP 1 α和HP 1 γ与染色质修饰复合物（如DPY 30）的特定组分相关。
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. Release of HP1γ from anchoring by Senp7 increases reprogramming efficiency HP1γ switches enrichment from histone H1 to histone H3.3 in pluripotent cells HP1γ interacts with OCT4 and DPPA4 independent of HP1α, HP1β, and H3K9 methylation Proteomic characterization of HP1 protein family in pluripotent cells In this article, Sridharan and colleagues perform proteomic characterization of the heterochromatin protein 1 (HP1) family in reprogramming and pluripotency. Depletion of HP1γ or its interacting partner SENP7, which anchors it to heterochromatin, increased iPSC generation. In pluripotent cells, HP1γ is highly nucleoplasmic and enriched with histone H3.3. HP1γ interacts with OCT4 and DPPA4 independent of HP1α, HP1β, and H3K9 methylation. HP1α and HP1γ differ in association with specific components of chromatin-modifying complexes such as DPY30.
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