FoxP3 interacts with linker histone H1.5 to modulate gene expression and program Treg cell activity.
FoxP3 interacts with linker histone H1.5 to modulate gene expression and program Treg cell activity.
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DOI：
10.1038/gene.2011.31
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发表时间：
2011-10
影响因子：
5
通讯作者：
Su, L.
中科院分区：
文献类型：
--
作者：
Mackey-Cushman, S. L.;Gao, J.;Holmes, D. A.;Nunoya, J-I;Wang, R.;Unutmaz, D.;Su, L.
叉头框转录因子FoxP 3控制CD 4 + CD 25+调节性T（Treg）细胞的发育和功能。FoxP 3通过多种尚未明确定义的表观遗传机制调节Treg细胞中的基因表达。我们通过co-IP/MS鉴定了FoxP 3在人T细胞中的相互作用蛋白。我们发现FoxP 3通过亮氨酸拉链（LZ）结构域与连接体组蛋白H1.5相互作用。FoxP 3 LZ中两个独立的IPEX患者来源的单残基突变都消除了其与H1.5的相互作用。在功能上，FoxP 3和H1.5协同抑制人T细胞中的IL-2表达;并且H1.5表达的沉默抑制FoxP 3抑制IL-2表达的能力。我们表明，FoxP 3特异性地增强了IL-2启动子处的H1.5关联，但减少了其在CTLA 4启动子处的关联，这与相应启动子的较高或较低的组蛋白乙酰化相关。最后，人类Treg细胞中H1.5表达的沉默损害了Treg抑制靶T细胞的功能。我们的结论是FoxP 3与H1.5相互作用，改变其与靶基因的结合，以调节其表达并编程Treg功能。
The forkhead box transcription factor FoxP3 controls the development and function of CD4+CD25+ regulatory T (Treg) cell. FoxP3 modulates gene expression in Treg cells by multiple epigenetic mechanisms that are not clearly defined. We identified FoxP3 interacting proteins in human T cells by co-IP/MS. We discovered that FoxP3 interacted with linker histone H1.5 via the leucine zipper (LZ) domain. Two independent IPEX patient-derived single residue mutations in the LZ of FoxP3 both abrogated its interaction with H1.5. Functionally, FoxP3 and H1.5 cooperatively repressed IL-2 expression in human T cells; and silencing of H1.5 expression inhibited the ability of FoxP3 to suppress IL-2 expression. We show that FoxP3 specifically enhanced H1.5 association at the IL-2 promoter, but reduce its association at the CTLA4 promoter, correlated with higher or lower histone acetylation of the respective promoters. Finally, silencing of H1.5 expression in human Treg cells impaired the Treg function to suppress target T cells. We conclude that FoxP3 interacts with H1.5 to alter its binding to target genes to modulate their expression and to program Treg function.
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影响因子：
64.8
作者：
Marson, Alexander;Kretschmer, Karsten;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Sakaguchi, S
DOI：
10.1073/pnas.0700298104
发表时间：
2007-03-13
影响因子：
11.1
作者：
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通讯作者：
Greene, Mark I.
影响因子：
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作者：
Fan, YH;Nikitina, T;Skoultchi, AI
通讯作者：
Skoultchi, AI