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首页> 外文期刊>Molecular and Cellular Biology >Two Histone/Protein Acetyltransferases, CBP and p300, Are Indispensable for Foxp3+ T-Regulatory Cell Development and Function
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Two Histone/Protein Acetyltransferases, CBP and p300, Are Indispensable for Foxp3+ T-Regulatory Cell Development and Function

机译：两种组蛋白/蛋白质乙酰基转移酶CBP和p300是Foxp3 + T调节细胞发育和功能所不可或缺的

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T-regulatory (Treg) cells are important to immune homeostasis, and Treg cell deficiency or dysfunction leads to autoimmune disease. A histone/protein acetyltransferase (HAT), p300, was recently found to be important for Treg function and stability, but further insights into the mechanisms by which p300 or other HATs affect Treg biology are needed. Here we show that CBP, a p300 paralog, is also important in controlling Treg function and stability. Thus, while mice with Treg-specific deletion of CBP or p300 developed minimal autoimmune disease, the combined deletion of CBP and p300 led to fatal autoimmunity by 3 to 4 weeks of age. The effects of CBP and p300 deletion on Treg development are dose dependent and involve multiple mechanisms. CBP and p300 cooperate with several key Treg transcription factors that act on the Foxp3 promoter to promote Foxp3 production. CBP and p300 also act on the Foxp3 conserved noncoding sequence 2 (CNS2) region to maintain Treg stability in inflammatory environments by regulating pCREB function and GATA3 expression, respectively. Lastly, CBP and p300 regulate the epigenetic status and function of Foxp3. Our findings provide insights into how HATs orchestrate multiple aspects of Treg development and function and identify overlapping but also discrete activities for p300 and CBP in control of Treg cells.
机译：T调节（Treg）细胞对免疫稳态很重要，Treg细胞缺乏或功能障碍会导致自身免疫性疾病。最近发现组蛋白/蛋白质乙酰基转移酶（HAT）对Treg的功能和稳定性很重要，但是需要进一步了解p300或其他HAT影响Treg生物学的机制。在这里，我们显示CBP（p300同源物）在控制Treg功能和稳定性方面也很重要。因此，虽然具有 CBP 或 p300 的Treg特异性缺失的小鼠发生了最小的自身免疫病，但 CBP 和 p300 < / em>在3至4周龄时导致致命的自身免疫。 CBP和p300缺失对Treg发育的影响是剂量依赖性的，涉及多种机制。 CBP和p300与几个关键的Treg转录因子协同作用，这些因子可作用于 Foxp3 启动子，从而促进Foxp3的产生。 CBP和p300还分别作用于Foxp3保守非编码序列2（CNS2）区，以通过调节pCREB功能和GATA3表达来维持Treg在炎性环境中的稳定性。最后，CBP和p300调节Foxp3的表观遗传状态和功能。我们的发现为HAT如何协调Treg发育和功能的多个方面提供了见识，并确定了p300和CBP在控制Treg细胞方面的重叠但离散活动。

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